The DOI matches its Crossref record; 88 of the 92 references it cites were found in a registry or an index; none of the 53 sources its claims cite is checked for support yet.
NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases
Open accessAbstract
Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Mitochondrial dysfunction is linked to oxidative stress and reactive oxygen species (ROS) in neurotoxicity during AD. Impaired mitochondrial metabolism has been associated with mitochondrial dysfunction in brain damage of AD. While the role of NADPH oxidase 4 (NOX4), a major source of ROS, has been identified in brain damage, the mechanism by which NOX4 regulates ferroptosis of astrocytes in AD remains unclear. Here, we show that the protein levels of NOX4 were significantly elevated in impaired astrocytes of cerebral cortex from patients with AD and APP/PS1 double-transgenic mouse model of AD. The levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), a marker of oxidative stress-induced lipid peroxidation, were significantly also elevated in impaired astrocytes of patients with AD and mouse AD. We demonstrate that the over-expression of NOX4 significantly increases the impairment of mitochondrial metabolism by inhibition of mitochondrial respiration and ATP production via the reduction of five protein complexes in the mitochondrial ETC in human astrocytes. Moreover, the elevation of NOX4 induces oxidative stress by mitochondrial ROS (mtROS) production, mitochondrial fragmentation, and inhibition of cellular antioxidant process in human astrocytes. Furthermore, the elevation of NOX4 increased ferroptosis-dependent cytotoxicity by the activation of oxidative stress-induced lipid peroxidation in human astrocytes. These results suggest that NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
NOX4 protein is elevated in impaired astrocytes in AD patient cortex and APP/PS1 mouse cortex, where lipid peroxidation markers 4-HNE and MDA are also increased. In human astrocytes, NOX4 overexpression impairs mitochondrial metabolism, induces oxidative stress and antioxidant suppression, and promotes ferroptosis-like lipid peroxidation and cytotoxicity.
Key findings
- NOX4 levels were significantly elevated in GFAP-positive impaired astrocytes in AD cortex versus non-AD cortex (n = 3 per group, n = 10 images per subject; p < 0.01) and in APP/PS1 mouse cortex versus WT (n = 5 per group, n = 10 images per subject; p < 0.01).
- Oxidative stress-induced lipid peroxidation markers 4-HNE and MDA were significantly elevated in impaired astrocytes of AD patients and APP/PS1 mice, and 4-HNE co-localized with NOX4-positive astrocytes (p < 0.01).
- In human astrocytes, NOX4 overexpression significantly suppressed basal and oligomycin/FCCP-responsive oxygen consumption rate, reduced mitochondrial ATP production, and reduced protein levels of all five mitochondrial ETC complexes: Complex I NDUFB8, Complex II SDHB, Complex III UQCRC2, Complex IV MTCO1, and Complex V ATP5F1A (p < 0.05 or p < 0.01).
- NOX4 overexpression increased mtROS and mitochondrial fragmentation, reduced GSH and GSH/GSSG, increased GSSG, inhibited NRF2 nuclear translocation and HO-1/GCL, and increased 4-HNE, MDA, iron accumulation, morphological cell death, and LDH cytotoxicity (p < 0.05 or p < 0.01).
Methods
- Postmortem human brain tissues: 12 paraffin-embedded tissues from 3 AD donors (frontal, occipital, temporal, parietal cortex) and 4 normal adult brain tissues from 4 donors; immunofluorescence analyzed NOX4, 4-HNE, MDA, GFAP, and Tomm20. APP/PS1 double-transgenic mice were compared with WT mice.
- Human astrocytes were transduced with pCMV6-AC-GFP-NOX4 or vector. Assays included Seahorse XF96e OCR and real-time ATP rate, immunoblot for mitochondrial ETC complexes, MitoSOX flow for mtROS, GSH/GSSG and GSSG measurements, NRF2 nuclear/cytosolic fractionation, HO-1 and GCL levels/activity, iron colorimetric assay, LDH cytotoxicity, and 3D imaging.
- Statistics used Shapiro-Wilk and Levene’s tests, two-tailed Student’s t-test for two groups, and ANOVA with Dunnett’s post hoc for multiple groups; significance was p < 0.05, p < 0.01, or p < 0.001.
Limitations
- Stated: it remains unclear whether the impaired astrocytes with high NOX4 have reactive astrocyte function in AD, and further study is needed on the role of NOX4 in reactive astrocytes. The authors also state that further study is needed to identify secreted molecules from NOX4-induced ferroptosis as potential diagnostic markers.
- Evident from the text: the human sample is small (3 AD donors and 4 normal donors), and the mechanistic causality in human astrocytes relies mainly on NOX4 overexpression; the text does not report NOX4 knockdown, NOX4 inhibition, or ferroptosis-blockade rescue experiments.
- Evident from the text: APP/PS1 mouse data are descriptive immunofluorescence comparisons, without in vivo NOX4 manipulation reported.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
58 Own result · 40 Not checked yet · 20 Own interpretation · 4 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We demonstrate that the over-expression of NOX4 significantly increases the impairment of mitochondrial metabolism by inhibition of mitochondrial respiration and ATP production via the reduction of five protein complexes in the mitochondrial ETC in human astrocytes.”
- Also stated in: § Introduction · plain
“We found that the elevation of NOX4 promotes the impairment of mitochondrial metabolism by inhibition of mitochondrial respiration and ATP production in human astrocytes.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), a marker of oxidative stress-induced lipid peroxidation, were significantly also elevated in impaired astrocytes of patients with AD and mouse AD.”
- Also stated in: § Introduction · plain
“The levels of 4-HNE and MDA were also significantly elevated in impaired astrocytes of patients with AD and mouse AD.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), a marker of oxidative stress-induced lipid peroxidation, were significantly also elevated in impaired astrocytes of patients with AD and mouse AD.”
- Also stated in: § The levels of oxidative stress-induced lipid peroxidation are elevated in impaired astrocytes of the cortex region from patients with Alzheimer's diseases · hedged
“These results suggest that the levels of oxidative stress-induced lipid peroxidation are elevated in impaired astrocytes of patients with AD.”
- Also stated in: § The levels of oxidative stress-induced lipid peroxidation are elevated in impaired astrocytes of the cortex region from patients with Alzheimer's diseases · plain
“The levels of 4-HNE and MDA were generally higher in every individual patient with AD.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § The levels of oxidative stress-induced lipid peroxidation are elevated in impaired astrocytes of the cortex region from patients with Alzheimer's diseases · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We demonstrate that the over-expression of NOX4 significantly increases the impairment of mitochondrial metabolism by inhibition of mitochondrial respiration and ATP production via the reduction of five protein complexes in the mitochondrial ETC in human astrocytes.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the elevation of NOX4 induces oxidative stress by mitochondrial ROS (mtROS) production, mitochondrial fragmentation, and inhibition of cellular antioxidant process in human astrocytes.”
- Also stated in: § Introduction · plain
“The elevation of NOX4 induced mtROS production and mitochondrial fragmentation in human astrocytes.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we show that the protein levels of NOX4 were significantly elevated in impaired astrocytes of cerebral cortex from patients with AD and APP/PS1 double-transgenic mouse model of AD.”
- Also stated in: § Introduction · plain
“Here, our results showed that the levels of NOX4 were significantly elevated in impaired astrocytes in patients with AD and APP/PS1 double-transgenic mouse model of AD.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the elevation of NOX4 induces oxidative stress by mitochondrial ROS (mtROS) production, mitochondrial fragmentation, and inhibition of cellular antioxidant process in human astrocytes.”
- Also stated in: § Introduction · plain
“The elevation of NOX4 induced mtROS production and mitochondrial fragmentation in human astrocytes.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the elevation of NOX4 increased ferroptosis-dependent cytotoxicity by the activation of oxidative stress-induced lipid peroxidation in human astrocytes.”
- Also stated in: § Introduction · plain
“Notably, the elevation of NOX4 induced ferroptosis-dependent cytotoxicity by the activation of lipid peroxidation in human astrocytes.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), a marker of oxidative stress-induced lipid peroxidation, were significantly also elevated in impaired astrocytes of patients with AD and mouse AD.”
- Also stated in: § Introduction · plain
“The levels of 4-HNE and MDA were also significantly elevated in impaired astrocytes of patients with AD and mouse AD.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, the number of impaired astrocytes which have the positive subcellular co-localization between NOX4 and GFAP was significantly increased in patients with AD (AD) (Fig. 1C).”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The levels of NOX4 are elevated in impaired astrocytes of the cortex region from patients with Alzheimer's diseases
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 5
- Probably not a substantial claim. 35
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the length of GFAP-positive filaments was shortened and the shape of GFAP-positive filaments showed shrinkage in astrocytes of patients with AD (AD) compared to non-AD donor (Normal) (Fig. 1A).”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The levels of NOX4 are elevated in impaired astrocytes of the cortex region from patients with Alzheimer's diseases
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NOX4 produces ROS constitutively [37].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [37] Serrander, 2007, NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation, Biochem. J. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The impairment of mitochondrial ETC activity in mitochondrial metabolism leads to an increase of reactive oxygen species (ROS) production which occurs mainly at Complex I and Complex III [31].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [31] Nemoto, 2000, Role for mitochondrial oxidants as regulators of cellular metabolism, Mol. Cell Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Among NOX isoforms, NOX4 is a major isoform in astrocytes [36].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [36] Nayernia, 2014, New insights on NOX enzymes in the central nervous system, Antioxidants Redox Signal. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The excessive production of ROS and the activation of lipid peroxidation are linked to ferroptosis-dependent cell death [32,33].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [32] Stockwell, 2017, Ferroptosis: a regulated cell death Nexus linking metabolism, Redox Biol. Dis. Cell
- Not checked yetcites [33] Stockwell, 2020, The chemistry and biology of ferroptosis, Cell Chem Biol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data are random, independent, normally distributed, and have a common variance.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Materials and methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Loss of supportive function by impaired astrocytes has been implicated in neurodegenerative diseases via neuronal death [21,22].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [21] Phatnani, 2015, Astrocytes in neurodegenerative disease, Cold Spring Harb Perspect Biol source
- Not checked yetcites [22] Karkkainen, 2012, Brain environment and Alzheimer's disease mutations affect the survival, migration and differentiation of neural progenitor cells, Curr. Alzheimer Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Recent studies suggest that oxidative stress is a critical factor that contributes to the initiation and progression of AD [[2], [3], [4]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [[2], [3], [4]]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Mitochondrial dysfunction plays an important role in the pathogenesis of AD as an early feature of AD [5,6].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [5] Perez Ortiz, 2019, Mitochondrial dysfunction in Alzheimer's disease: role in pathogenesis and novel therapeutic opportunities, Br. J. Pharmacol. source
- Not checked yetcites [6] Wood, 2020, Mitochondrial dysfunction manifests in the early stages of Alzheimer disease, Nat. Rev. Neurol.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Recent studies have shown the impairment of mitochondrial metabolism by multiple mitochondrial alterations in major neurodegenerative diseases such as AD and Parkinson's disease (PD) [[11], [12], [13]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [[11], [12], [13]]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mitochondrial damage has been found to be involved in lipid peroxidation and imbalance of iron homeostasis in neurodegenerative diseases such as AD and PD [34].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Introduction
What the sources say
- Not checked yetcites [34] Conrad, 2018, Regulation of lipid peroxidation and ferroptosis in diverse species, Genes Dev. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To ensure objectivity, all measurements were performed with blinded conditions by two observers per experiment under identical conditions.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Materials and methods > Immunofluorescence analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“NOX4 is linked to oxidative stress and ROS production in brain injury [42,43].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [42] Casas, 2017, NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage, Proc. Natl. Acad. Sci. U. S. A. source
- Not checked yetcites [43] Ma, 2018, Deletion of NADPH oxidase 4 reduces severity of traumatic brain injury, Free Radic. Biol. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Mitochondrial dysfunction has been associated with the pathogenesis of AD [5,6].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [5] Perez Ortiz, 2019, Mitochondrial dysfunction in Alzheimer's disease: role in pathogenesis and novel therapeutic opportunities, Br. J. Pharmacol. source
- Not checked yetcites [6] Wood, 2020, Mitochondrial dysfunction manifests in the early stages of Alzheimer disease, Nat. Rev. Neurol.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Oxidative stress is linked to amyloid-beta (Aβ) toxicity in AD [44,45].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The levels of cerebral blood (CBF) and cerebral metabolic rate for oxygen (CMRO2) in the medial temporal region were decreased in patient with AD [38].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [38] Ishii, 1996, Decreased medial temporal oxygen metabolism in Alzheimer's disease shown by PET, J. Nucl. Med.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In APP/PS1 mouse model of AD, the elevation of NOX activity is linked to cognitive impairment [47].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [47] Bruce-Keller, 2011, Cognitive impairment in humanized APP×PS1 mice is linked to Aβ(1-42) and NOX activation, Neurobiol. Dis. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Since NOX4 is a constitutively active form among the NOX isoforms, the activity of NOX4 depends on its expression [37].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [37] Serrander, 2007, NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation, Biochem. J. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the high levels of ceramide contribute to formation of amyloid β-peptides [[81], [82], [83]]”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [81], [82], [83]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“the role of lipid peroxidation has been discovered in cell dysfunction and death during neuronal degeneration [74,75]”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [74] Mattson, 1998, Modification of ion homeostasis by lipid peroxidation: roles in neuronal degeneration and adaptive plasticity, Trends Neurosci. source
- Not checked yetcites [75] Keller, 1998, Roles of lipid peroxidation in modulation of cellular signaling pathways, cell dysfunction, and death in the nervous system, Rev. Neurosci. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“High levels of 4-HNE found in pathological conditions or diseases which are associated with cellular stress and dysfunction, cellular damage and pro-apoptotic signaling [[68], [69], [70], [71], [72], [73]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [68], [69], [70]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Ferroptosis-derived dead cells can release damage-associated molecular patterns (DAMPs) and lipid metabolites that can cause an elevation of inflammation [76,77].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Reactive aldehydes from lipid peroxidation have biological active functions [59].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [59] Esterbauer, 1991, Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes, Free Radic. Biol. Med. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The high production of ROS is associated with excessive intracellular lipid accumulation such as diacylglycerol (DAG) and ceramide [[78], [79], [80]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [78], [79], [80]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A previous study has shown that a product of lipid peroxidation is increased in brain of patients with AD [55].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [55] Markesbery, 1998, Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease, Neurobiol. Aging source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The role of reactive astrocytes remains unclear in terms of plaque formation, Aβ clearance and plaque growth restriction [50,51].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Also, mitochondrial dysfunction including the excessive production of mtROS contributes to the induction of neuronal apoptosis [[84], [85], [86]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [84], [85], [86]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For immunoblots, β-actin was used as a loading control.”
- Also stated in: § NOX4-induced mitochondrial metabolic impairment induces oxidative stress by inhibition of cellular antioxidant process in human astrocytes · plain
“For immunoblots, Histone H3 (nuclear) and β-actin (cytosolic) was used as a loading control.”
- Also stated in: § NOX4 promotes ferroptosis by oxidative stress-induced lipid peroxidation in human astrocytes · plain
“For immunoblots, β-actin was used as a loading control.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The elevation of NOX4 promotes oxidative stress by impairment of mitochondrial metabolism via inhibition of mitochondrial respiration and ATP production in human astrocytes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § NOX4-induced mitochondrial metabolic impairment induces oxidative stress by inhibition of cellular antioxidant process in human astrocytes · plain
In the paper
“The redox imbalance and oxidative stress are linked to neurodegeneration in AD [[1], [2], [3], [4]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [1], [2], [3]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the accumulation of ceramide may have the effects of neurotoxicity in AD”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data are representative of three independent experiments.”
- Also stated in: § NOX4-induced mitochondrial metabolic impairment induces oxidative stress by inhibition of cellular antioxidant process in human astrocytes · plain
“Data are representative of three independent experiments.”
- Also stated in: § The elevation of NOX4 promotes oxidative stress by impairment of mitochondrial metabolism via inhibition of mitochondrial respiration and ATP production in human astrocytes · plain
“Data are representatives of three independent experiments.”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The elevation of NOX4 promotes oxidative stress by impairment of mitochondrial metabolism via inhibition of mitochondrial respiration and ATP production in human astrocytes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Also stated in: § NOX4-induced mitochondrial metabolic impairment induces oxidative stress by inhibition of cellular antioxidant process in human astrocytes · plain
In the paper
“4-HNE, an electrophilic lipid peroxidation product, also has various cytotoxic effects of lipid peroxidation such as depletion of glutathione, dysfunction of structural proteins, reduction in enzyme activities, and induction of cell death [60].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [60] Craighead, 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Based on hormetic effects of 4-HNE, low physiological levels of 4-HNE can provide positive effects on cell function including cell proliferation and signaling pathway such as tyrosine kinase receptor (TKR) activation and downstream kinase signaling [[61], [62], [63], [64], [65], [66], [67]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [61], [62], [63]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In pathogenesis of neurodegenerative diseases, the high levels of 4-HNE are involved in oxidative stress of AD or Parkinson's diseases [[70], [71], [72], [73]].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [70], [71], [72]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The abundant diffusible products of lipid peroxidation are chemically reactive aldehydes including malondialdehyde (MDA), acrolein, 4-hydroxy-2-hexenal (4-HHE), and 4-hydroxy-2-nonenal (4-HNE) [57,58].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [57] Schneider, 2001, Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals, J. Biol. Chem. source
- Not checked yetcites [58] Porter, 1995, Mechanisms of free radical oxidation of unsaturated lipids, Lipids source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Similarly, a recent study has suggested that NOX4 in pericytes is the major source of ROS which is involved in the constriction of capillaries early in the response to Aβ [48].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [48] Nortley, 2019, Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes, Science source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Regarding the form of astrocytes, reactive astrocytes are an activated form of astrocytes in response to toxic materials [49].”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Discussion
What the sources say
- Not checked yetcites [49] Wilhelmsson, 2006, Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury, Proc. Natl. Acad. Sci. U. S. A. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The mechanisms by which NOX4 regulates ferroptosis of astrocytes by oxidative stress via impairment of mitochondrial metabolism in AD remain unclear.
“However, the mechanisms by which NOX4 regulates ferroptosis of astrocytes by oxidative stress via impairment of mitochondrial metabolism in AD remains unclear.”
The paper relies on this without support.
4-HNE is a marker for ferroptosis.
“Since the levels of 4-HNE, a marker for ferroptosis, were elevated in impaired astrocytes of patients with AD”
The paper relies on this without support.
Iron accumulation is a specific marker of ferroptosis.
“the accumulation of iron, a specific marker of ferroptosis”
The paper relies on this without support.
APP/PS1 mice model AD.
“APP/PS1 double-transgenic mouse model of AD”
The paper relies on this without support.
NRF2 is a key regulator of the cellular antioxidant response.
“nuclear factor erythroid 2–related factor 2 (NRF2) signaling pathway, a key regulator of the cellular antioxidant response”
The paper relies on this without support.
HO-1 and GCL are target genes of NRF2.
“heme oxygenase-1 (HO-1) (Fig. 6E and F) and glutamate cysteine ligase (GCL) (Fig. 6E and F) as target genes of NRF2”
The paper relies on this without support.
Mitochondrial fragmentation indicates mitochondrial impairment.
“We next analyzed morphological impairment of mitochondria caused by NOX4 over-expression through immunofluorescence staining with Tomm20”
The paper relies on this without support.
The upstream molecular target in the regulation of ferroptosis by lipid peroxidation in Alzheimer's disease remains unclear.
“the upstream molecular target in the regulation of ferroptosis by lipid peroxidation in AD remains unclear”
The paper relies on this without support.
NOX4 levels are high in the cortex of patients with Alzheimer's disease.
“the high levels of NOX4, in cortex of patients with AD”
The paper relies on this without support.
It is unclear whether impaired astrocytes in Alzheimer's disease have a function of reactive astrocytes.
“it was unclear whether these impaired astrocytes have a function of reactive astrocytes in AD”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The levels of two products of oxidative damage, 4-HNE and MDA, were also significantly elevated, suggesting that the elevation of NOX4 promotes the impairment of mitochondrial metabolism, mitochondrial ROS production and fragmentation in human astrocytes [101].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [101]
In the citing paper
“Ferroptosis-dependent cytotoxicity induced by the activation of OS has also been described in human astrocytes from AD patients [101].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [101]
In the citing paper
“NO X4 is the astrocytes isoform, and its levels are reported significantly elevated in astrocytes of patients with AD and APP/PS1 double-transgenic mouse model of AD [101].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [101]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Materials and methods > Human subjects study
“A total of four paraffin embedded adult normal brain tissues from four donors including frontal cortex (NBP2-77761), occipital cortex (NBP2-77766), temporal cortex (NBP2-77774) and parietal cortex (NBP2-77769) were obtained from Novus Biologicals”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The levels of NOX4 are elevated in impaired astrocytes of the cortex region from patients with Alzheimer's diseases
“(B) Quantification of intensity for NOX4 positive staining in astrocytes from immunofluorescence images in the cerebral cortex region from patients with AD (AD #1, AD #2, AD #3) or non-AD (normal) (n = 3 per group, n = 10 images per individual subject).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Materials and methods > Reagents and antibodies
“polyclonal rabbit anti-4-HNE antibody (ab3517, Abcam, Cambridge, UK)”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Materials and methods > Immunofluorescence analysis
“polyclonal rabbit anti-4-HNE antibody (1:100) (ab46545, Abcam, Cambridge, UK)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The elevation of NOX4 promotes oxidative stress by impairment of mitochondrial metabolism via inhibition of mitochondrial respiration and ATP production in human astrocytes
“(G) Quantification of cells with mitochondrial fragmentation from immunofluorescence images of mitochondrial morphology in control (Control) and NOX4 overexpressing (NOX4) human astrocytes (n = 10 per group).”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The elevation of NOX4 promotes oxidative stress by impairment of mitochondrial metabolism via inhibition of mitochondrial respiration and ATP production in human astrocytes
“(The percent of morphological dead cells in a total of 100 cells of 10 individual images per group was calculated).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The levels of oxidative stress-induced lipid peroxidation are elevated in impaired astrocytes of the cortex region from brains of APP/PS1 mice
“Immunofluorescence staining revealed that the intensity of 4-HNE-positive staining in GFAP-positive astrocytes was increased of the cortex region of APP/PS1 mice compared to WT mice (Fig. 4A and C and Fig. S6).”
§ NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases > Results > The levels of oxidative stress-induced lipid peroxidation are elevated in impaired astrocytes of the cortex region from brains of APP/PS1 mice
“(B) Quantification of 4-HNE positive staining in astrocytes from immunofluorescence images in the cortex region from brains of APP/PS1 mice (APP/PS1) or wild-type mice (WT) (n = 5 per group, n = 10 images per individual subject). Data are mean ± standard deviation (SD). **, p < 0.01 by Student's two-tailed t-test. (C) Quantification of 4-HNE positive astrocytes”
Citations
Cites
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695 · cited 2×
“Ferroptosis is a type of programmed cell death that is dependent on iron and the accumulation of lipid peroxides, mainly lipid hydroperoxides, which cause damage to the lipid bilayer of the plasma membrane through accelerated oxidation of membrane lipids [32,33].”
BackgroundThe NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · cited 3×
“In most mammals, there are seven NOX isoforms (NOX1, NOX2, NOX3, NOX4, NOX5, dual oxidase (DUOX)1, and DUOX2) [35].”
BackgroundInfluentialChemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes
Esterbauer, H., Schaur, R. J., & Zollner, H. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90192-6 · Cited by 6,672
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Oxidative Stress, Glutamate, and Neurodegenerative Disorders
Coyle, J. T., & Puttfarcken, P. (1993) · Science · doi:10.1126/science.7901908 · Cited by 3,762
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Neurodegenerative diseases and oxidative stress
Barnham, K. J., Masters, C. L., & Bush, A. I. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1330 · Cited by 3,683
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088 · cited 1×
“As the driving force of ferroptosis, a high level of lipid peroxidation can disrupt cellular function [56].”
BackgroundOxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383 · cited 1×
“Oxidative stress is characterized by the over-production of reactive oxygen species (ROS), damage of the mitochondrial respiratory chain, and imbalance of Ca2+ homeostasis [9,10].”
Background
Research works printed but not linked: 1
- Stockwell, 2017, Ferroptosis: a regulated cell death Nexus linking metabolism, Redox Biol. Dis. Cell, 171, 273
Cited by
Sorted by citations
Items 401–500 of 679
Lu, S., Yao, Z., Cheng, Q., Wu, J., Jiang, Y., & Lin, H. (2024) · The Turkish Journal of Gastroenterology · doi:10.5152/tjg.2023.23300 · Cited by 6
The mechanism of 14-3-3η in thyroxine induced mitophagy in cardiomyocytes
Cui, Y., Zhang, Y., Dai, S., Wan, S., Guan, H., Wang, D., Jin, B., Xiao, W., & Liu, F. (2024) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2024.112271 · Cited by 6
Joshi, A., Giorgi, F. M., & Sanna, P. P. (2024) · eNeuro · doi:10.1523/eneuro.0118-24.2024 · Cited by 6
“NOX4 (NADPH oxidase 4) has been shown by Park et al. (2021) to promote ferroptosis in non-neuronal cells via oxidative stress-induced lipid peroxidation by dysregulation of metabolism of mitochondria; we found it to be upregulated in all AD stages, but its log-fold change is maximum in endothelial…”
BackgroundLi, J., Ning, Z., Zhong, X., Hu, D., Wang, Y., Cheng, X., & Deng, M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e38068 · Cited by 6
“Elevated NOX4 can cause oxidative stress-induced lipid peroxidation and mitochondrial metabolic disorders [30].”
Macías, F., Ulloa, M., Clapp, C., de la Escalera, G. M., & Arnold, E. (2024) · PLoS ONE · doi:10.1371/journal.pone.0313328 · Cited by 6
Chen, Y., Tian, Y., Guan, B., et al. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1605513 · Cited by 6
NOX2 Contributes to High‐Frequency Outer Hair Cell Vulnerability in the Cochlea
Qi, M., Gao, Z., Qiu, Y., Wang, R., Tian, K., Yue, B., Zhang, X., Zhang, P., Wu, Z., Zhu, Q., et al. (2025) · Advanced Science · doi:10.1002/advs.202408830 · Cited by 9
Zhu, X., Chen, Y., Xu, B., Mou, J., Wang, M., Gu, Q., Sun, Q., Li, M., Zhao, C., Zeng, M. Y., et al. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.08.036 · Cited by 7
Identification of a key ceRNA network associated with ferroptosis in gastric cancer
Wen, J., Liu, J., Yang, J., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-24402-3 · Cited by 6
Papadimitriou‐Tsantarliotou, A., Avgeros, C., Konstantinidou, M., & Vizirianakis, I. S. (2024) · IUBMB Life · doi:10.1002/iub.2897 · Cited by 5
“179 Similar studies in DKC1 silenced fibroblasts confirmed these results.”
García-Salas, R., Cilleros-Holgado, P., Spirito, A. D., Gómez-Fernández, D., Piñero-Pérez, R., Romero-Domínguez, J. M., Álvarez-Córdoba, M., Reche-López, D., Romero-González, A., López-Cabrera, A., et al. (2025) · Aging · doi:10.18632/aging.206198 · Cited by 8
Shi, X., Xu, W., Xue, Y., et al. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177759 · Cited by 5
The emerging role of disulfidptosis in Alzheimer's disease
Zhou, Q., Zheng, N., Chen, Z., Xie, L., Yang, X., Sun, Q., Lin, J., Li, B., & Li, L. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178085 · Cited by 10
Wang, Z.-J., Liang, Y., Ren, Y.-F., et al. (2025) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2025.11.003 · Cited by 5
Dang, K., Zheng, Q., Zhou, T., Wang, Y., Pan, D., Du, L., Suo, S., Dang, Y., Ma, L., & Gao, X. (2025) · Food Chemistry · doi:10.1016/j.foodchem.2025.147028 · Cited by 5
Advances in fluorescent probe design and imaging applications for Alzheimer's disease biomarker
Li, Y., Liu, H., Yin, C., & Huo, F. (2025) · Dyes and Pigments · doi:10.1016/j.dyepig.2025.113411 · Cited by 5
Shi, Y., Li, F. Z., Zhao, T., et al. (2026) · Advanced Science · doi:10.1002/advs.202516477 · Cited by 5
“It is noteworthy that oxidative stress is closely related to ferroptosis because of a similar pathological process, and the crosstalk between oxidative stress and ferroptosis has been studied in some diseases, including ischemic stroke [ 17 ] and Alzheimer’s disease [ 18 ].”
Öz, M. A., Şimşek, H., Özdemir, S., et al. (2026) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70223 · Cited by 5
Yu, W., Zhuang, S., Zhan, M., Chen, Y., Zhang, J., Chen, L., Tu, C., Zheng, L., & Shi, C. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231193 · Cited by 6
A Novel BD2-Selective Inhibitor of BRDs Mitigates ROS Production and OA Pathogenesis
Lee, H., Choe, J., Son, M., et al. (2024) · Antioxidants · doi:10.3390/antiox13080943 · Cited by 5
Liu, X., Chen, G., Yang, Y., Liu, F., Wu, G., An, L., Tang, T. A., & Zhang, J. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.119371 · Cited by 5
Shen, X., Cheng, H., Zheng, J., et al. (2025) · Molecular Carcinogenesis · doi:10.1002/mc.70006 · Cited by 5
“In the context of central nervous system diseases, ferroptosis has been linked to numerous conditions, including cerebral ischemia/reperfusion [9], neurodegenerative diseases [10], and brain tumors [11].”
Wang, D., Zhang, C., Guo, H., Cui, T., Pu, W., Huang, B., Zhu, J., & Dai, X. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04144-1 · Cited by 5
Advancements in Single-Cell RNA Sequencing Research for Neurological Diseases
Yang, B., Hu, S., Jiang, Y., Xu, L., Shu, S., & Zhang, H. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04126-3 · Cited by 6
Liu, Y., Chen, H., Wu, Y., et al. (2024) · Inhalation Toxicology · doi:10.1080/08958378.2024.2335193 · Cited by 5
“As a by-product of lipid peroxidation, 4-hydroxynonenal (4-HNE) is regarded as a stable marker of oxidative stress (Park et al. 2021).”
BackgroundRole of astrocytes in Alzheimer's disease pathogenesis and the impact of exercise-induced remodeling
Shao, J., Deng, Q., Feng, S., Wu, C., Liu, X., & Yang, L. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150418 · Cited by 5
Wang, J., Yang, J., Lu, J., Lu, J., Bai, L., Song, Y., & Chen, G. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04701-2 · Cited by 5
Chen, J., Guo, G., Wang, X., Li, Z., Ji, T., Li, Y., Dong, H., Zhang, H., & Gao, M. (2025) · Toxics · doi:10.3390/toxics13040258 · Cited by 5
“In human astrocytes, Nox4 inhibits mitochondrial respiration and ATP production, which, in turn, leads to mitochondrial dysfunction and promotes oxidative stress [37].”
OxInflammation in Alzheimer’s disease
Cervellati, C., Zuliani, G., & Valacchi, G. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.374144 · Cited by 5
“Notably, recent findings point to a causal role of NOX4 also in tau pathology (Park et al., 2021; Luengo et al., 2022).”
BackgroundLyu, S., Wang, H.-R., & Ma, T.-J. (2023) · Molecules · doi:10.3390/molecules28124853 · Cited by 5
“MDA was the main by-product of lipid peroxidation and an important indicator of oxidative damage in cells [31].”
BackgroundJi, F., Lee, H., & Kim, J. H. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.04.605473 · Cited by 5
“This process is closely related to the expression of 4-HNE and MDA, as both compounds are markers of lipid peroxidation (He et al., 2022; Park et al., 2021).”
BackgroundSelf-citationLiu, B., Jin, Q., Sun, Y., Yang, Z. M., Meng, P., Zhang, X., Chen, Q., Gan, P., Zhao, T., He, J., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1563362 · Cited by 7
Ru, Z., Wu, Y., Qu, Q., Miao, Y., Zhu, L., & Hu, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-08968-2 · Cited by 4
“The metabolic changes driven by oxidative stress are vital in ferroptosis 53 .”
Gupta, N., & Singh, K. (2025) · Journal of Molecular Histology · doi:10.1007/s10735-025-10507-2 · Cited by 6
“Enzymes such as lipoxygenase (LOX), cyclo-oxygenase (COX), XO and NADPH oxidase (NOX family), are prominent generators of ROS (Park et al. 2021; Zeng et al. 2017 ).”
Gao, X., Liang, X., Gao, L., Zhang, Y., Zhang, L., Jia, S., Zhang, B., & Meng, C. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123882 · Cited by 4
Niño-Rivero, S., Cabral, R., Fleitas, J., Alcalde-Ahlig, L., Castaño, E. M., Morelli, L., McGregor, R., Galeano, P., & Lagos, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262210944 · Cited by 5
“Third, subsets of A1-like astrocytes produce reactive oxygen and nitrogen species and engage pathways associated with lipid peroxidation and ferroptosis, processes shown to occur in astrocytes and to promote lo-cal oxidative damage and synaptic vulnerability [63–66].”
Gong, Z., Guo, D., Lin, Y., Liu, Z., Lv, M., Liu, X., Sun, M., Wang, L., Zhao, T., Wang, Z., et al. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05542-9 · Cited by 5
“Research on Alz-heimer's disease (AD) showed that NOX4 promoted ferrop-tosis in astrocytes by impairing mitochondrial metabolism and facilitating oxidative stress-induced lipid peroxidation [44].”
Ginsenoside Rb1 targets the NRF2-PPARγ-ACSL4 axis to inhibit PTECs ferroptosis
Tan, B., Wu, Z., Wang, S., Tan, W., Lin, L., Yang, X., Zheng, L., Li, J., Li, K., Yang, J., et al. (2026) · Chinese Medicine · doi:10.1186/s13020-025-01292-x · Cited by 5
“Considering NOX4’s established role in ferroptosis through ROS generation [37], we posit that Rb1’s anti-ferroptotic effects may mechanistically contribute to its benefits in early CKD progression.”
Rewiring Brain Recovery: Astrocyte–Neuron Metabolic Cooperation in Stroke
Lu, W., Jiang, Z., & Wen, J. (2026) · Antioxidants and Redox Signaling · doi:10.1177/15230864251411183 · Cited by 5
“However, recent studies have identi fi ed NOX4 as a major source of ROS and a key contributor to brain damage (Park et al., 2021).”
Lipid droplets and major metabolic disorders
Dechert, W. J., & He, G. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11563-x · Cited by 5
Zhang, Y., Zhang, D., & Xiao, H. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261430002 · Cited by 5
Ferroptosis Exists in Ischemia Reperfusion Injury after Cardiac Surgery with Cardiopulmonary Bypass
Zhang, S., Li, J., Wang, J., Chen, X., Shu, G., Feng, D., & Zheng, X. (2024) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-024-01228-6 · Cited by 4
“The end-products of lipid per-oxidation, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), have been shown to be toxic to cells by impairing mitochondrial metabolism [11].”
Gao, J., Dong, Y.-Y., Jin, X., Dai, L., Wang, J.-R., & Zhang, H. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s455337 · Cited by 4
Comprehensive review of perioperative factors influencing ferroptosis
Fan, C.-H., Zeng, X., Feng, R.-M., Yi, H.-W., & Xia, R. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117375 · Cited by 4
MiR-29b inhibits COC expansion and oocyte in vitro maturation via induction of ROS by targeting CYCS
Zhan, X., Qi, N., Toms, D., Freiburger, R., Fletcher, L., Wang, B., & Li, J. (2024) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2024.107598 · Cited by 4
Guo, S., Gong, Z., Sun, X., et al. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s475645 · Cited by 4
Altered metabolic function induced by Aβ‐oligomers and PSEN1 mutations in iPSC ‐derived astrocytes
Elsworthy, R. J., Finelli, M. J., Aqattan, S., Dunleavy, C., King, M. C., Ludlam, A., Tarczyluk, M. A., Allen, S., Prosser, S., Chen, R., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16267 · Cited by 7
The Molecular Interplay Between p53-Mediated Ferroptosis and Non-Coding RNAs in Cancer
Punziano, C., Trombetti, S., Grosso, M., Tornesello, M. L., & Faraonio, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146588 · Cited by 5
“In addition to POR, H 2 O 2 production during ferroptosis can occur by specific enzymatic reactions performed by NOX enzymes [6,19], as well as during the mitochondrial election transport chain (ETC) (reviewed in [20]).”
Cai, Y., Huang, G., Shan, C., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157262 · Cited by 4
Detection of Ferroptosis in Models of Brain Diseases
Shen, D., Yang, F., & Li, Q. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3433-2_21 · Cited by 4
Aleksandrova, Y. R., & Неганова, М. Е. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914766 · Cited by 4
Yue, C., Lian, W., Duan, M., et al. (2023) · Environmental Toxicology · doi:10.1002/tox.24051 · Cited by 4
RetractedObacunone regulates ferroptosis in ovarian cancer through the Akt/p53 pathway
Zhao, Y., Liang, H., & Cui, X. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03738-9 · Cited by 4
“Cells were treated with various concentrations of OB (0, 10, 20, and 40 μM) (Park et al. 2021) in each well and subsequently incubated at 37 ℃ of 24 h. Add 10 μL of the Cell Counting kit 8 (CCK8; C0037, Beyotime, CHN) reagent to each well and incubate at 37 ℃ for 2 h. Absorbance should be measured…”
Lu, Z., Jiang, J., Yao, X., & Hou, G. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117226 · Cited by 5
Du, W., Yu, S., Liu, R., Kong, Q., Hao, X., & Liu, Y. (2025) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02291-7 · Cited by 5
“…to impaired energy metabolism, increased oxidative stress, and dysregulated calcium homeostasis, ultimately contributing to neuronal degeneration and cognitive decline (Calvo-Rodriguez and Bac-skai 2021; Park et al. 2021; Song et al. 2021; Baracaldo-Santamaría et al. 2023; Zhang et al. 2023b).”
Qin, G., Song, R., Sun, J. J., Dai, J., Wang, W., Meng, F., Wang, D., Liu, Z., Sun, B., & Li, C. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s499852 · Cited by 5
Gui, Q., Luo, W., Wu, D., Liu, J., Zhou, D., Zhu, X., Wu, M., & Zhu, L. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152115 · Cited by 4
Therapeutic correlation of NOX4 and diabetes-mediated neurodegeneration
Tiwari, C., Khan, H., Grewal, A. K., & Singh, T. G. (2023) · Obesity Medicine · doi:10.1016/j.obmed.2023.100515 · Cited by 4
Zhang, Y., Fang, H., Wang, T., Zhang, Z., Zhu, T., Xiong, L., Hu, H., & Liu, H. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300334 · Cited by 5
Deng, Z., Dong, Z., Wang, Y., Dai, Y., Liu, J., & Deng, F. (2024) · Human Genetics · doi:10.1007/s00439-024-02641-w · Cited by 5
“(Nor-malization and batch effect removal occasionally result in negative values, indicative of relative changes in gene expression levels) The results show that expression levels of TACSTD2, BTG2, SOCS3, PDK4, NOX4, APOE, STAT1, SOD1 , and CD44 had significantly higher in CP-AKI.”
InfluentialWang, L., Tang, Z., Deng, Y., Peng, Y., Xiao, Y. C., Xu, J., Ni, R., & Qi, X. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.12.523781 · Cited by 4
New insights into ovarian regression-related mitochondrial dysfunction in the late-laying period
Gu, T., Liu, J., Zeng, T., Chen, L., Tian, Y., Xu, W., & Lu, L. (2025) · Poultry Science · doi:10.1016/j.psj.2025.104938 · Cited by 4
“Mitochondrial dysfunction is characterized by exacerbated ROS production and oxidative stress (Chen et al., 2024a, 2024b), which activates the ferroptosis pathway (Cacciottola et al., 2021; Nemati et al., 2019; Park et al., 2021).”
Richards, S. E. V., Yang, M., Deik, A. A., & Ricq, E. L. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04463-2 · Cited by 3
Wang, X., Cui, L., Kong, L., Zou, S.-F., & Zhao, X. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.107219 · Cited by 3
Gunnarsdottir, S. H., Rehrl, J., Sepperer, T., Haretzmüller, L., Sesink, D., Löwenstein, K., Gadermayr, M., Hölzl, C., Stelzhammer, B., Himmelsbach, M., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-06105-7 · Cited by 3
“This mechanism is closely associated with the exacerbation of dermatological conditions such as psoriasis and acne 38,40,41 .”
Aldehyde Dehydrogenase 6 Family Member A1 Facilitates Ti Implant Osseointegration in Hyperlipidemia
Wang, Y., Yu, L., Liu, Y., Xu, X., Zhang, D., Liu, S., & Ge, S. (2025) · Oral Diseases · doi:10.1111/odi.15342 · Cited by 3
“Thus, developing a specific agonist of ALDH6A1 would be an effective way to further understand the biological activity of this enzyme and could provide a potential therapeutic strategy to disrupt the vicious circle of lipid peroxidation between ROS and MDA under hyperlipidemia conditions (Figure 8).”
InfluentialNOX4 facilitates diabetic cataract progression through the NF-κB signaling pathway
Su, W., Chen, L., Xie, P., et al. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110530 · Cited by 3
Chen, X., Pang, Y., Amona, F. M., Liu, Z., Wang, F., Yuan, L., Yang, J., Zhang, W., Fang, X., & Chen, X. (2025) · Journal of Virology · doi:10.1128/jvi.00954-25 · Cited by 4
“While oxidative stress and ferroptosis are interconnected due to similar pathological processes, as previously reported (8, 9, 54, 55), comprehen sive research on their crosstalk in PRRSV infection is lacking.”
Zhong, J., Li, M., Dai, Z., & Wan, J. (2025) · Neurochemistry International · doi:10.1016/j.neuint.2025.106049 · Cited by 3
Liu, T., Fan, H., Lin, R.-X., Liu, A.-D., Feng, J.-C., Zeng, Y., Chen, H., Zhong, H., Xia, J.-C., Lin, X., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157601 · Cited by 4
Geng, X., Li, J., Wu, B., Wang, W., Li, Z., Liu, S., Li, H., & Chang, H. (2026) · Cancer Cell International · doi:10.1186/s12935-025-04151-9 · Cited by 7
Ge, X., Meng, Q., Liu, J., Wang, E., Liu, X., Shi, S., Gong, X., Liu, Z., Han, W., & Zhou, X. (2026) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2026.130912 · Cited by 4
da Silva‐Araújo, E. R., Toscano, A. E., Gouveia, H. J. C. B., Pontes, P. B., dos Santos, J. P., dos Santos, O. H., de Lemos, M. D. T. B., Melo, N. C. D. O., de Melo, J. V., Hernández, E. P., et al. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101427 · Cited by 4
“Elevated 4-HNE, together with MDA and NADPHoxidase-4, has been shown to impair mitochondrial ATP generation in the cerebral cortex, as demonstrated in genetically modified Alzheimer ’ s models [69].”
Dong, Z., Zhang, Z., Peng, Y., Chen, Z., Lin, L., Chen, B., Zhao, M., Gong, M., Wang, G., Aa, J., et al. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158170 · Cited by 3
Peng, X., Zhou, Y., Chen, J., et al. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.04.038 · Cited by 3
Harnessing ferroptosis from multilayer defense networks to nanoplatforms for specific cancer therapy
Xu, X., Wang, X., Jiang, W., Kamaruddin, W. H. A., Fang, C., & Zhang, P. (2026) · BMEMat · doi:10.1002/bmm2.70080 · Cited by 5
Zhao, Y., Fu, J., Zhao, P., Jiang, Y., Wang, Y., Zhang, Y., Li, Z., Zhao, Y., Li, N., Lang, B., et al. (2026) · Cell Death Discovery · doi:10.1038/s41420-026-03147-2 · Cited by 6
Yang, Q., Jin, L., Ding, Q., Hu, W., Zou, H., Xiao, M., Chen, K., Yu, Y., Shang, J., Huang, X., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9252319 · Cited by 3
“RNA-induced oxidative stress is closely related with disease progression [16, 17].”
BackgroundRetractedYang, Y., Yan, Z., Xie, Q., et al. (2024) · Aging · doi:10.18632/aging.205708 · Cited by 3
Du, Z., Shi, Y. Y., & Tan, J. (2024) · Briefings in Functional Genomics · doi:10.1093/bfgp/elae025 · Cited by 3
Neurogliovascular alterations in brain pathologies across lifespan
Daigle, B., Bevilacqua, L. M., Noël, V. P., Lebel, M., Côté, D. C., Lévesque, L., & Ménard, C. (2024) · Glial health research. · doi:10.1016/j.ghres.2024.100004 · Cited by 4
Zhang, J., Wang, X., Guo, L., et al. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101761 · Cited by 3
“NOX4 is the major source of cellular ROS, and its overactivation would lead to increased oxidative stress [45,46].”
Teneligliptin and empagliflozin attenuate ferroptosis-mediated acute tubular injury
Ema, C., Iwakura, T., Tsuji, T., Nakayama, Y., Tsuchida, M., Kitamura, A., Katahashi, N., Ishigaki, S., Isobe, S., Fujikura, T., et al. (2025) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaf203 · Cited by 3
Ma, X., Han, L., Xu, M., Feng, Y., Liu, C., Zhao, Y., Zhang, M., Xu, G., & Sun, X. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47110895 · Cited by 3
“MDA, a product of lipid peroxidation in cell membranes, serves as a reliable biomarker for oxidative stress [34].”
Chen, K.-Y., Chen, Y., Cheng, C.-J., et al. (2023) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2023.04.007 · Cited by 3
Sun, Z., Zhang, X., Dong, Y., Liu, Y., Wang, C., Li, Y., Ma, C., Xu, G., Wang, S., Yang, C.-T., et al. (2024) · Brain Sciences · doi:10.3390/brainsci14020161 · Cited by 4
Wang, S., Gong, X., Yuan, J., Huang, J., Zhao, R., Ji, J., Wang, M., Shi, X., Xin, W., Zhong, Y., et al. (2024) · Environmental Pollution · doi:10.1016/j.envpol.2024.125085 · Cited by 3
Elsworthy, R. J., Finelli, M. J., Aqattan, S., Dunleavy, C., King, M. C., Ludlam, A., Allen, S. L., Prosser, S., Chen, R. E., Martínez‐Jarquín, S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.23.554346 · Cited by 2
Du, Y., Wu, H., Zhan, S., Zhang, R., Zhang, G., & Bu, N. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04392-0 · Cited by 2
“Ferroptosis is driven by the accu - mulation of lipid-based reactive oxygen species closely related to oxidative stress and cystine metabolism [ 53].”
Sardari, M., Sahafi, O. H., & Rezayof, A. (2025) · Brain Research · doi:10.1016/j.brainres.2025.150040 · Cited by 3
Chen, P., Shi, T., Hu, D., Su, X., Jin, J., Chen, M., Wang, H., & Chen, W. (2025) · The Kaohsiung Journal of Medical Sciences · doi:10.1002/kjm2.70157 · Cited by 3
“The binding of AGEs to RAGE increases reactive oxygen species (ROS) generation and induces oxidative stress-induced lipid peroxidation, thereby leading to increased ferroptosis-dependent cytotoxicity [13].”
Chen, J., Chen, Y., Chen, W., Yingjie, T., Wang, T., Xie, Y., Wang, B., & Luo, J. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112352 · Cited by 2
Yuan, F., Han, Z., Yang, S., Chen, J., Li, R., Zhang, Z., Song, J., Wang, D., & Ban, Y. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1758041 · Cited by 5
Li, X., Wu, Z., Yao, C. H., Zhang, P., Zhu, Q., Nan, S., Xiao, L., & Qi, S. (2026) · Research · doi:10.34133/research.1163 · Cited by 3
“Elevated NOX4 levels promote the generation of mtROS, which down-regulates PPAR-α and leads to mitochondrial breakdown and cellular oxidation processes [ 43 ].”
Qi, W., Wang, J., Wang, S., Shi, X., Xiong, T., Li, R., Zheng, W., Liu, M., Deng, S., Huang, Q., et al. (2026) · Bioactive Materials · doi:10.1016/j.bioactmat.2026.01.039 · Cited by 3
“S84-87), which confers a significant advantage in the treatment of MI. Mitochondrial lipid membranes are usually damaged by high levels of mtROS, releasing malondialdehyde (MDA); therefore, MDA is often used to assess mitochondrial membrane damage [37].”
Yang, S., Wu, J., Song, X., Jiang, H., Zou, Y., Lei, Z., & Ge, J. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.02.014 · Cited by 3
Xu, X., Wang, Q., Liu, Z., Li, J., Wang, S., & Qian, L. (2026) · Antioxidants · doi:10.3390/antiox15050571 · Cited by 4
“Studies in glial cells have further demonstrated that abnormal NOX4 upregulation suppresses the levels of certain protein complexes in the mitochondrial ETC, thereby directly impairing mitochondrial respiratory function [74].”
Qin, S., Zhan, X., Sun, H., Liu, Y., Zhang, Y., Zhang, W., Liu, D., Liu, F., Xue, Y., Zhu, E., et al. (2026) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6c02594 · Cited by 2
Zhao, K.-H., Fang, X.-T., Zhu, Y.-T., et al. (2026) · Phytochemistry · doi:10.1016/j.phytochem.2026.115028 · Cited by 2
Savcı, A. (2022) · International Food Research Journal · doi:10.47836/ifrj.29.5.09 · Cited by 2
“Peroxidation, which occurs as a result of the reaction of free radicals with lipids, leads to various diseases (Park et al., 2021).”
Background
Metadata
- Authors
- Park, M. W., Cha, H. W., Kim, J., Kim, J. H., Yang, H., Yoon, S., Boonpraman, N., Yi, S. S., Yoo, I. D., & Moon, J.-S.
- Affiliations
- Soonchunhyang University (KR)
- Soonchunhyang University Hospital Cheonan (KR)
- Corresponding author
- Yoo, Ik Dong
- Moon, Jong-Seok
- ORCID
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 41
- Pages
- 101947
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC8027773
- OpenAlex
- W3136661179
- Cited by
- 683
- References
- 92
- Citations by year
- 2026: 139 · 2025: 145 · 2024: 187 · 2023: 128 · 2022: 74 · 2021: 10
- FWCI
- 62.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Soonchunhyang University
- National Research Foundation of Korea
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- NOX4, ferroptosis, astrocytes, Alzheimer's disease, oxidative stress, lipid peroxidation, mitochondrial dysfunction, mitochondrial respiration, mitochondrial electron transport chain, mitochondrial reactive oxygen species, mitochondrial fragmentation, 4-hydroxynonenal, malondialdehyde, APP/PS1 mice, reactive oxygen species
- MeSH terms
- NADPH Oxidase 4, Ferroptosis, Alzheimer Disease, Animals, Astrocytes, Humans, Mitochondria, Lipid Peroxidation, Reactive Oxygen Species, Oxidative Stress, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
