Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain

In the paper

“Inhibiting SGK activity completely nullifies the effects of neutrophil survival factors, leading to a delayed resolution of inflammation. However, this does not alter the recruitment of neutrophils to sites of inflammation within the body”

What the sources say

• Disputed

  The Results report that SGK1 inhibition increased, rather than delayed, inflammation resolution (genetic inhibition section; page unavailable). They also report that inhibition blocked survival induced by GM-CSF and hypoxia, but not by LPS or ATPγs (human neutrophil survival section). Recruitment was unchanged after genetic knockdown, although the inhibitor GSK650394 reduced it through apparent off-target effects. (LLM, conf=0.92)

  Checked by a reasoning model — may be wrong.

  cites Burgon et al., 2014 sourceExperimental — accuracy not yet measured

In the paper

“SGK1 impacts blood pressure regulation. This effect is significant within the blood-brain barrier”

What the sources say

• ?Not checked — no full text of the sourcecites Faresse et al., 2012 source
• Partly supported

  The Discussion reports that SGK1 contributes to high-glucose-induced changes in ion transport in blood-brain barrier endothelial cells. It does not report an effect on blood pressure regulation; searches for blood pressure and hypertension found no such finding in our copy. (LLM, conf=0.86)

  cites Klug et al., 2021 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Zhang et al., 2022a

In the paper

“One study analyzing mouse SGK1 cDNA reports the conservation of seven in-frame methionine codons (ATG) in the N-terminus across various vertebrates, including humans, mice, frogs, and sharks (Arteaga et al., 2007). Alternative translation initiation from these conserved codons in the N-terminus produces four distinct SGK1 isoforms”

What the sources say

• Partly supported

  The section “Alternative Translation Initiation Produces Four Sgk1 Isoforms” reports seven in-frame methionine codons in mouse Sgk1 and four isoforms produced by alternative initiation. But Table 1 shows that not all seven codons are conserved across the listed vertebrates, and the section “Endogenous Sgk1 in Mouse Cells and in Tissues Expresses as Several Isoforms” reports at least three isoforms for human and frog Sgk1, not four. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites Arteaga et al., 2007 sourceExperimental — accuracy not yet measured

In the paper

“Moreover, it significantly influences cell growth, proliferation, survival, migration, and apoptosis”

What the sources say

• ?Not checked — no full text of the sourcecites Amato et al., 2009 source
• Supported

  The Introduction links SGK1 to cellular survival and to regulation of apoptosis, migration, and proliferation; it also discusses tumor growth. The section on SGK1 knockdown reports significant effects on apoptosis and proliferation in intestinal epithelial cells. Together, these passages support the broad claim about cell growth and survival-related processes. (LLM, conf=0.88)

  cites Bai et al., 2015 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lang et al., 2010a

In the paper

“In the activation process of SGK1, extracellular stimuli induce the activation of mTORC2, which phosphorylates Ser422 on SGK1’s hydrophobic motif (Garcia-Martinez and Alessi, 2008). Subsequently, 3-Phosphoinositide-Dependent Protein Kinase-1 (PDK1) is recruited to the phosphorylated Ser, leading to the transfer of a phosphate group to Thr256 within the kinase domain of SGK1 (Biondi et al., 2001),”

What the sources say

• Supported

  The Figure 7 mechanism describes insulin and growth factors stimulating SGK1 hydrophobic-motif phosphorylation via mTORC2, and the figure identifies Ser422 as the phosphorylated site. The subsequent PDK1 step in the citing sentence is attributed to Biondi et al., not to this source. (LLM, conf=0.91)

  cites Garcia-Martinez and Alessi, 2008 source
• Supported

  The Introduction identifies Thr256 as SGK1’s T-loop residue and states that PDK1 phosphorylates SGK at its T-loop. The Discussion reports that phosphorylation of SGK1’s Ser422 hydrophobic motif promotes its interaction with PDK1 and subsequent T-loop phosphorylation. The mTORC2 step has a different citation in the citing sentence and is not attributed to this paper. (LLM, conf=0.90)

  cites Biondi et al., 2001 source
• ?Not checked — no full text of the sourcecites Akhoon et al., 2019 source

In the paper

“The activated SGK1 then rapidly stimulates the ENaC, enhancing the driving force for the secretion of other ion transport, such as potassium (K+)”

What the sources say

• Supported

  The Discussion (page unavailable) states that SGK1-dependent ENaC activation increases the driving force for potassium transport through ROMK channels and possibly BK channels. The Methods describe measuring ENaC-dependent current one hour after potassium stimulation, consistent with the claim’s rapid-response wording. (LLM, conf=0.90)

  cites Saha et al., 2022 source

In the paper

“Additionally, WNK1 interacts with chloride ions (Cl−) to alter its conformation, facilitating the capture of SGK1 (Piala et al., 2014; Terker et al., 2015). This conformational change promotes the interaction between Mammalian Target of Rapamycin Complex 2 (mTORC2) and SGK1 and enhances the phosphorylation of SGK1 while simultaneously inhibiting the kinase activity of WNK1.”

What the sources say

• Partly supported

  The Abstract and Results report that chloride binds WNK1, stabilizes its inactive conformation, and inhibits its autophosphorylation and activation. The Introduction mentions that WNK1 activates SGK1, but our copy does not support the claimed chloride-dependent capture of SGK1, increased mTORC2–SGK1 interaction, or enhanced SGK1 phosphorylation. No page numbers are available in our copy. (LLM, conf=0.88)

  cites Piala et al., 2014 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and Results section on extracellular potassium and WNK kinases report that chloride binds WNK1 and inhibits its activation, and test mutations at its chloride-binding sites. The cited paper does not describe a chloride-induced conformational change that captures SGK1, promotes mTORC2–SGK1 interaction, or enhances SGK1 phosphorylation. (LLM, conf=0.88)

  cites Terker et al., 2015 sourceExperimental — accuracy not yet measured

In the paper

“Serum/Glucocorticoid Regulated Kinase 1 (SGK1), a member of the AGC kinase family (cAMP-dependent, cGMP-dependent, and protein kinase C), is a serine/threonine kinase that exhibits extensive expression in a majority of tissues”

What the sources say

• Partly supported

  The Discussion says h-sgk transcripts were expressed in all human tissues analyzed, supporting widespread expression. It describes h-sgk as encoding a *putative* serine/threonine protein kinase, so the unqualified kinase characterization is stronger than this paper establishes. (LLM, conf=0.82)

  cites Waldegger et al., 1997 sourceExperimental — accuracy not yet measured
• Partly supported

  The paper describes sgk as a member of the serine/threonine protein kinase gene family and reports that its mRNA is expressed in most adult rat tissues (opening summary; page not provided). The claim broadens that finding to SGK1 expression in most tissues generally, whereas the cited evidence concerns mRNA in adult rats. (LLM, conf=0.86)

  cites Webster et al., 1993 sourceExperimental — accuracy not yet measured

In the paper

“Similar to other AGC protein kinases, SGK1 possesses a kinase domain featuring a pocket that recognizes hydrophobic motifs containing phosphoserine/phosphothreonine. This pocket achieves recognition through phosphorylation of two oppositely positioned arginine and lysine residues. This structural characteristic enables SGK1’s distinct substrate affinity in biological processes”

What the sources say

• Partly supported

  The Abstract and Introduction state that SGK1 has a phosphate-binding pocket that interacts with its own phosphorylated hydrophobic motif and stimulates kinase activity. The Discussion says oppositely positioned arginine or lysine residues bind the motif’s phosphate; it does not say those residues are phosphorylated. These passages do not establish the claimed distinct substrate affinity. (LLM, conf=0.90)

  cites Frodin et al., 2002 sourceExperimental — accuracy not yet measured

In the paper

“It’s noteworthy that astrocytes play a signaling hub in stress-induced changes in brain glucose metabolism, with SGK1 being a factor in formation of aversive memories”

What the sources say

• Partly supported

  The Abstract and Results identify astrocytes as important for glucocorticoid-dependent aversive memory and show that SGK1 regulates glucose uptake in astrocytes. The Discussion proposes that this pathway may affect stress-induced memory formation, but does not establish SGK1 itself as a factor in aversive memory formation. (LLM, conf=0.86)

  cites Tertil et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“LTP in the hippocampus is closely associated with the phosphorylation of SGK1 at Ser422. Introducing a dominant-negative SGK1 targeting Ser422, disrupts LTP with regional specificity in the brain”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ma et al., 2006
• Partly supported

  The Introduction (page unavailable) reports increased SGK1 phosphorylation at Ser422 after protocols that induce hippocampal LTP, and says SGK1 inhibition impairs LTP expression but not induction. It does not report that a Ser422-targeting dominant-negative SGK1 disrupts LTP with regional specificity. The Results concern region-dependent dendritic spine changes, while the Discussion says regional effects on synaptic function and plasticity remain to be tested. (LLM, conf=0.88)

  cites Steffke et al., 2020 sourceExperimental — accuracy not yet measured

In the paper

“In contrast, SGK1 acts as an effective negative regulator in TLR-induced inflammation. Pharmacological inhibition or suppression using small interfering RNA (siRNA) of SGK1 enhances the production of pro-inflammatory cytokines (such as TNF, IL-12, and IL-6) in monocytes bound to TLR”

What the sources say

• Supported

  The Results report that pharmacological SGK1 inhibition increased IL-12, TNF, and IL-6 in LPS-stimulated human monocytes (Fig. 2A–D), and that SGK1 siRNA knockdown increased the same cytokines (Fig. 3C). The Discussion identifies SGK1 as a negative regulator of TLR-mediated immune responses. (LLM, conf=0.95)

  cites Zhou et al., 2015 source

In the paper

“In the dentate gyrus, increased SGK1 activity promotes the maturation of dendritic spines. However, the effect is opposite in the CA1 region”

What the sources say

• Supported

  The Results section ('Overexpression of SGK1 in DG drives increased mushroom spine density') states that increasing SGK1 activity promotes dendritic spine maturation in the dentate gyrus, in contrast to CA1. The CA1 Results section reports that inhibiting endogenous SGK1 activity increased mature mushroom spines, supporting the opposite effect there. (LLM, conf=0.94)

  cites Steffke et al., 2020 source

In the paper

“Specifically, SGK1 increases neuronal plasticity by modulating the activity of transcription factors SRF and CREB1. This process allows transitioning stored information from short-term memories to long-term memories”

What the sources say

• ?Could not verify

  The Introduction (page not available) discusses Zif268 and object-recognition memory reconsolidation, not SGK1. Searches for SGK1, SRF, CREB1, and short-term-to-long-term memory transition found no passage in our copy addressing the attributed mechanism. (LLM, conf=0.76)

  cites Gonzalez et al., 2019 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Tyan et al., 2008 source

In the paper

“However, the pathological states differ significantly across various neurological diseases, and the alterations in SGK1 also vary, leading to distinct impacts of SGK1 on different diseases. Even within the same disease, the influence of SGK1 on its progression can vary”

What the sources say

• Partly supported

  The Results (page unavailable) show that SGK1 overexpression worsened tau pathology and memory in Tg601 mice. The References list a study reporting improved memory and amyloid pathology with SGK1 overexpression in a different Alzheimer’s mouse model, offering some support for variation within one disease. This paper does not establish that differing pathological states and SGK1 alterations cause distinct effects across neurological diseases. (LLM, conf=0.78)

  cites Elahi et al., 2021 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Lian et al., 2020 source

In the paper

“Interestingly, NDRG1 is activated during myelination in developmental stages and in the remyelination process following myelin damage in adult mice”

What the sources say

• Supported

  The Abstract reports NDRG1 expression during developmental myelination and during remyelination after cuprizone-induced demyelination of the adult corpus callosum. The Results describe increasing NDRG1 levels during developmental myelination (Figure 1F–G). (LLM, conf=0.94)

  cites Marechal et al., 2022 source

In the paper

“Interaction of these proteins lead to the formation of an SGK1-GSK-3β-Tau complex, contributing to abnormal Tau tangles and ultimately resulting in disintegrating microtubules in neurons”

What the sources say

• Partly supported

  The Results section ('SGK1-mediated tau phosphorylation at Ser214 and GSK-3ß activation'; page unavailable) describes a scaffold-like SGK1–GSK-3β–tau complex and increased tau aggregation and fibril formation. It reports reduced tubulin polymerization activity, but does not show that the complex causes neurofibrillary tangles or disintegrating microtubules in neurons. The Discussion says SGK1 might disassemble microtubules, rather than establishing that outcome. (LLM, conf=0.88)

  cites Elahi et al., 2021 sourceExperimental — accuracy not yet measured
• Partly supported

  Section 3 reports a tau–GSK-3β complex and links tau phosphorylation to reduced microtubule binding and neurofibrillary tangles. It does not identify SGK1 as part of that complex or establish the claimed sequence ending in disintegrating neuronal microtubules (searched for SGK1 and the three-protein complex). (LLM, conf=0.86)

  cites Sayas and Avila, 2021 sourceExperimental — accuracy not yet measured

In the paper

“Upon the knockdown of SGK1 in SH-SY5Y cells using siRNA, a downregulation of dopaminergic cells and an upregulation of α-syn expression were observed”

What the sources say

• Supported

  The Results (p. 5) report that SGK1 siRNA knockdown in SH-SY5Y cells decreased TH expression and increased α-syn expression; the authors interpret this as dopaminergic cell loss. The Discussion (p. 6) likewise reports increased α-syn expression and dopaminergic cell death after knockdown. (LLM, conf=0.93)

  cites Yeo et al., 2018 source

In the paper

“Mechanistically, SGK1 is a stress-responsive kinase, typically upregulated in cells undergoing stress or damage”

What the sources say

• Supported

  The “SGK1 and L-HPA Axis Activity” section describes SGK1 as involved in cellular stress response and reports increased expression under chronic stress and after neuronal injury. It also notes exceptions after acute stress, which is consistent with the claim’s qualifier “typically.” Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites Dattilo et al., 2020 source

In the paper

“Pharmacological inhibition and silencing of SGK1 can ameliorate pathological synuclein aggregation and PD-related behavioral deficits in various in vitro and in vivo MPTP-induced PD models. Moreover, this intervention protects midbrain dopaminergic neurons from degeneration”

What the sources say

• Partly supported

  The Results report that SGK1 inhibition or silencing reduced synuclein pathology and protected midbrain dopamine neurons across PD models; inhibitor treatment also improved behavioral deficits in MPTP-treated mice. However, the Methods distinguish the MPTP mouse model from the synuclein-induced model, and the Results describe the aggregation experiments in synuclein-based models—not as various in vitro and in vivo MPTP-induced models. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites Kwon et al., 2021 sourceExperimental — accuracy not yet measured

In the paper

“Simultaneously, SGK1 maintains stable levels of BACE1 (β-secretase) and Cofilin, indicating its influence does not involve promoting the amyloidogenic β pathway”

What the sources say

• ?Could not verify

  The Amyloidogenesis section identifies BACE1 as the β-secretase involved in Aβ production, but does not address SGK1’s effect on that pathway. Searches for SGK1 and Cofilin found no passage reporting stable levels of either protein or drawing the claimed conclusion about SGK1. Page numbers were unavailable in our copy. (LLM, conf=0.76)

  cites Hampel et al., 2021 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Lian et al., 2020 source

In the paper

“This finding suggests SGK1 may promote the expression or activity of ADAM10 and IDE, thereby enhancing the metabolism of APP through the non-amyloidogenic β pathway and increasing the degradation of Aβ”

What the sources say

• Partly supported

  The Abstract and Discussion report that APP intracellular domain (AICD) promotes IDE expression and IDE-mediated Aβ degradation. They do not identify SGK1 or ADAM10 as drivers of those effects. The Introduction also describes non-amyloidogenic APP processing as an α- and γ-secretase pathway, not the β pathway printed in the citing sentence. (LLM, conf=0.88)

  cites Lauer et al., 2020 sourceExperimental — accuracy not yet measured

In the paper

“SGK1-related pathways regulate IL-6 expression in astrocytes, mitigating the loss of oligodendrocyte progenitor cells (OPCs)”

What the sources say

• Supported

  The Results section, “SCFAs Regulate IL-6 Expression via SGK1 In Vivo and In Vitro,” reports that SGK1 regulates IL-6 expression in astrocytes. The Discussion links IL-6 to OPC apoptosis and states that controlling IL-6 secretion is key to reducing OPC loss. The paper establishes this pathway in its SCFA-treated experimental models. (LLM, conf=0.89)

  cites Gao et al., 2022 source

In the paper

“Despite the elevated rate of myelin formation in AD mice, the overall myelin levels were reduced, suggesting the increased rate of myelin regeneration is insufficient to fully counterbalance the accelerated myelin degeneration”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Chen et al., 2021a
• Supported

  The “OPC-mediated demyelination and remyelination in AD” section reports increased remyelination in an AD mouse model alongside decreased overall myelination. It states that the increased rate of myelin formation cannot compensate for the increased rate of degeneration. (LLM, conf=0.95)

  cites Zou et al., 2023 source

In the paper

“In 3NP-treated mouse models, SGK1 expression levels rose 2.7-fold compared to controls, but treatment with cannabigerol resulted in a 1.41-fold decrease in SGK1 expression”

What the sources say

• Supported

  The ‘Study of Neuroprotective Effects of CBG in 3NP-lesioned Mice’ section reports 2.7-fold induction of Sgk1 in 3NP mice versus controls and significant −1.41-fold repression in 3NP mice treated with cannabigerol. Both figures match the claim. (LLM, conf=0.94)

  cites Valdeolivas et al., 2015 source

In the paper

“The beneficial effects of SGK1 inhibition may be related to its enhancement of neuroglial activity, which aids in the clearance of glutamate toxicity and prevents neuroglial cell senescence and mitochondrial damage”

What the sources say

• Supported

  The Discussion states that SGK1 inhibition potentiated glial glutamate clearance and relieved glial mitochondrial oxidative stress and senescence. The Results sections separately report increased glutamate uptake, reduced toxin-induced mitochondrial damage, and reduced markers of glial senescence. The claim’s tentative account of the beneficial effects matches those findings. (LLM, conf=0.94)

  cites Kwon et al., 2021 source

In the paper

“In the peripheral colonic tissues of PD groups, there is a notable decrease in the expression of SGK1, alongside an increase in α-syn expression. Additionally, suppressing SGK1 expression exacerbates the expression of genes associated with PD-related constipation”

What the sources say

• Partly supported

  The Discussion (§3) reports decreased SGK1 and increased α-syn in the colon of MPTP-induced PD mice. Results (§2.4) report that SGK1 knockdown in SW480 cells increased α-syn and Na+/K+ pump ATPase α1 expression, but the paper presents their connection to constipation as an inference, not a demonstrated exacerbation of constipation-related gene expression. (LLM, conf=0.85)

  cites Seo et al., 2023 sourceExperimental — accuracy not yet measured

In the paper

“Additionally, overexpression of SGK1 in cells enhances mitochondrial function and inactivates GSK3β, MKK4, and JNK, protecting cells from oxidative stress-induced damage”

What the sources say

• ?Not checked — no full text of the sourcecites Iqbal et al., 2015 source
• Partly supported

  Results §3.5 and the Discussion link SGK1 to mitochondrial function, GSK3β inactivation, and protection of H2O2-exposed HK-2 renal cells. The paper does not support the added claim that SGK1 inactivates MKK4 or JNK; its experiments also examine SGK1 knockdown rather than experimentally induced overexpression. (LLM, conf=0.88)

  cites Jiang et al., 2019 sourceExperimental — accuracy not yet measured

In the paper

“SGK1, related to Akt and activated by PI3K, is also involved in mediating survival signals”

What the sources say

• Supported

  The Abstract explicitly says SGKs are related to Akt, are activated by PI3K, and that SGK1 promotes cell survival. The Results further conclude that activated SGK may mediate PI3K survival effects alongside Akt. (LLM, conf=0.94)

  cites Brunet et al., 2001 source

In the paper

“After TBI, the loss of myelination can trigger neuroinflammation and upregulation of SGK1 transcription levels in oligodendrocytes”

What the sources say

• ?Not checked — no full text of the sourcecites Imaizumi et al., 1994 source
• Partly supported

  The Discussion (page unavailable) says TBI-related brain damage can lead to neuroinflammatory responses. It does not say that loss of myelination triggers those responses, or report increased SGK1 transcription in oligodendrocytes; searches for SGK1 and myelination found no supporting passage. (LLM, conf=0.86)

  cites Kempuraj et al., 2021 sourceExperimental — accuracy not yet measured

In the paper

“SGK1 facilitates M2 microglial polarization and aids in reducing post-ischemic microglial proliferation, diminishing neuroinflammation by activating the SGK1-CREB-FOXO3a pathway”

What the sources say

• Partly supported

  The Results (p. 11) report that Swell1 overexpression promotes M2 microglial polarization and reduces inflammatory factors after ischemic stroke. But the Discussion (p. 16) says Swell1 promotes—not reduces—resident microglial proliferation through the SGK1–CREB–FOXO3a pathway. The claim reverses that proliferation finding and attributes the broader effects to SGK1 alone rather than Swell1 activation. (LLM, conf=0.89)

  cites Chen et al., 2023 sourceExperimental — accuracy not yet measured

In the paper

“post-MCAO, the levels initially double compared to sham-operated rats at 6 hours before falling below control levels after 24 hours, accompanied by an increase in neuronal apoptosis”

What the sources say

• ?Not checked — no full text of the sourcecites Nishida et al., 2004 source
• Partly supported

  The discussion (page unavailable) reports that SGK1 levels rose transiently after MCAO and returned to control levels by 24 hours; it does not report that they fell below control. Figure 5 identifies a 6-hour measurement, but the supplied text does not establish a doubling at that time. The Results section reports increasing TUNEL-positive cells after reperfusion, supporting the apoptosis portion. (LLM, conf=0.88)

  cites Zhang et al., 2014 sourceExperimental — accuracy not yet measured

In the paper

“In rat hippocampal neurons, SGK1 levels significantly drop following OGD and further decline over time”

What the sources say

• ?Not checked — no full text of the sourcecites Nishida et al., 2004 source
• Supported

  In the results passage on OGD-induced apoptosis, western blotting showed that SGK1 protein levels in hippocampal neurons fell significantly after OGD and decreased further with increasing recovery time. The discussion likewise describes SGK1 expression as decreasing with OGD and continuing to decrease over time. (LLM, conf=0.94)

  cites Zhang et al., 2014 source

In the paper

“This finding underscores the critical role of SGK1 in VEGF-mediated angiogenesis, which plays a role in both stress-induced BBB dysfunction and the development of depressive-like behaviors”

What the sources say

• Partly supported

  The Abstract reports that VEGF/VEGFR2 contributes to stress-induced BBB permeability and depressive-like behavior in chronically stressed mice, and describes VEGF as a mediator of angiogenesis. It does not mention SGK1 or establish that SGK1 is critical to VEGF-mediated angiogenesis; nor does it show that angiogenesis itself causes the reported BBB and behavioral effects. (LLM, conf=0.88)

  cites Matsuno et al., 2022 sourceExperimental — accuracy not yet measured

In the paper

“activation of SGK1, which can increase cytoplasmic calcium levels, thereby compromising the integrity of the BBB”

What the sources say

• Partly supported

  The Conclusions (page unavailable) say that TRPC and TRPV channels mediate calcium influx at the BBB and may modulate barrier integrity. The Discussion (page unavailable) also links increased intracellular calcium and altered barrier permeability. Our copy does not identify SGK1 as the activator or establish that activating it compromises the BBB; searches for SGK1 and serum glucocorticoid-regulated kinase found no supporting passage. (LLM, conf=0.86)

  cites Brown et al., 2008 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Imai et al., 2003 source

In the paper

“SGK1-knockdow leads to increased infarct size and brain edema, promotes neuronal apoptosis, and reduces Nissl bodies in the rat MCAO model”

What the sources say

• Partly supported

  The knockdown results sections report larger infarcts, more brain swelling, and increased neuronal apoptosis in cold-saline-treated rats with MCAO. The Nissl-body finding is inconsistent: the results section says relative IOD increased, while the Discussion says it decreased. The experiments also concern rats receiving intracarotid cold saline infusion, a condition omitted from the claim. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  cites Wang et al., 2019 sourceExperimental — accuracy not yet measured

In the paper

“Currently, reports indicate that SGK1 is present in microglia (Inoue et al., 2016b), oligodendrocytes (Hinds et al., 2017), and astrocytes (Tertil et al., 2018).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Inoue et al., 2016b
• Supported

  The Hinds et al. citation is attached only to oligodendrocytes, not to microglia or astrocytes. The Results (Experiment 1, co-localization subsection) report that most Sgk1 mRNA in the corpus callosum after acute stress co-localized with Mbp mRNA, an oligodendrocyte marker. (LLM, conf=0.91)

  cites Hinds et al., 2017 source
• Supported

  The Results section reports induction of Sgk1 transcripts in isolated hippocampal astrocytes and examines SGK1 knockdown in primary astrocytes. The citation to Tertil et al. is attached specifically to astrocytes; the other cell types have separate citations. (LLM, conf=0.93)

  cites Tertil et al., 2018 source

In the paper

“It inhibits SGK1 by blocking ATP binding, suppressing its phosphorylation activity”

What the sources say

• Partly supported

  The Results section (Figure 6 and the accompanying text; page unavailable) reports that EMD638683 inhibits SGK1 activity and reduces SGK1-mediated tau phosphorylation. Neither those passages nor the Discussion establish that it works by blocking ATP binding, so the claimed mechanism is unsupported. (LLM, conf=0.88)

  cites Elahi et al., 2021 sourceExperimental — accuracy not yet measured

In the paper

“Inhibiting SGK1 might be an effective therapeutic strategy to curb glycogen accumulation, suppress mTOR activity, and rectify autophagy defects in Lafora disease”

What the sources say

• Supported

  The Discussion explicitly proposes suppressing SGK1 as a potential therapeutic approach to reduce glycogen accumulation, inhibit mTOR activity, and rescue autophagy defects in Lafora disease. It also says that SGK1 inhibitors still need to be tested in animal models, consistent with the claim’s tentative wording. (LLM, conf=0.95)

  cites Singh et al., 2013 source

In the paper

“In the neurological system, SGK1 is involved in regulating ion channels and transport proteins (Lang et al., 2014; Lang et al., 2010b), cell apoptosis (Martin-Batista et al., 2021a), proliferation and differentiation (Anacker et al., 2013), autophagy (Matteoni et al., 2019), and neuroinflammation (Wu et al., 2024).”

What the sources say

• Supported

  Lang et al. (2014) is cited for the ion-channel and transport-protein clause, not the later claims about apoptosis, autophagy, or neuroinflammation. The Abstract describes SGK1 regulation of carriers and ion channels, and the SGK1-sensitive channels section identifies effects in neurons, including regulation of the GluR6 receptor and possible effects on neuronal excitability. (LLM, conf=0.93)

  cites Lang et al., 2014 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Martin-Batista et al., 2021a
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2024

In the paper

“SGK1 has been extensively studied across a diverse array of neurological disorders”

In the paper

“This array includes neurodegenerative diseases (e.g., Alzheimer’s disease, Huntington’s disease and Parkinson’s disease), brain injuries (e.g., cerebral ischemia and traumatic brain injury), psychiatric conditions (e.g., depression and drug addiction), as well as chronic neurological disorders such as epilepsy.”

In the paper

“The SGK1 gene in the human genome is located on chromosome 6 at the 6q23 region, spans 148,867 bases, and contains 14 coding exons. It encodes the SGK1 protein, which comprises 431 amino acids and has a molecular mass of approximately 49 kDa”

What the sources say

• ?Not checked — no full text of the sourcecites Waldegger et al., 1998 source
• ?Not checked — no full text of the sourcecites Zhao et al., 2007 source

In the paper

“In the inactive form of SGK1, the αC helix typical in other structures is absent. Instead, the segment corresponding to the C helix forms a β-strand. This strand is stabilized by a short anti-parallel β-sheet from the N-terminal segment of the activation loop”

What the sources say

• ?Not checked — no full text of the sourcecites Zhao et al., 2007 source

In the paper

“SGK1 is emerging as an increasingly compelling therapeutic target across the spectrum of neurological disorders, supported by the availability of several effective agents.”

In the paper

“However, in disease states, a deletion mutation in the SGK1 gene resulting in the loss of the first 60 amino acids at the N-terminus prevents effective ubiquitination and subsequent degradation by the 26S proteasome. This effect leads to an abnormally high steady-state level of the mutated SGK1 protein”

What the sources say

• ?Not checked — no full text of the sourcecites Brickley et al., 2002 source

In the paper

“WNK1 (With No Lysine −1) activates the SGK1, which, in turn, leads to the activation of the ENaC”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al., 2005

In the paper

“However, the conclusions of many studies observing the prevalence and function of SGK1 in neurological disorders are contradictory, necessitating a review of the SGK1 research within neurological disorders.”

In the paper

“It holds a crucial position in managing a variety of ion channels, membrane carriers, transcriptional factors or regulators, and cellular enzymes, as well as in controlling neuronal excitability”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lang et al., 2010a

In the paper

“It’s noteworthy that in many cell types, endogenous SGK1 is typically present at very low levels”

What the sources say

• ?Not checked — no full text of the sourcecites Brickley et al., 2002 source

In the paper

“An increasing number of studies indicate that SGK1 plays a role in enhancing memory formation and reducing the production of Aβ, highlighting its potential in the treatment of AD”

What the sources say

• ?Not checked — no full text of the sourcecites Lian et al., 2020 source
• ?Not checked — no full text of the sourcecites Tyan et al., 2008 source

In the paper

“Overexpression of SGK1 receptors in the dorsal hippocampus enhances memory, which correlates with a significant increase in the expression of SGK1 and the mRNA of hippocampal glutamate receptor subunits GluA1 and GluA2”

What the sources say

• ?Not checked — no full text of the sourcecites Lengel et al., 2022 source

In the paper

“As the name suggests, SGK1 is regulated by serum and glucocorticoid levels”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lang et al., 2009a

In the paper

“These findings define the importance of SGK1’s role in regulating ion transport and maintaining osmotic balance within the brain.”

In the paper

“SGK1 upregulates the expression of postsynaptic density protein-95 (PSD-95) in the hippocampus, which facilitates the expression of LTP in hippocampal neurons”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ma et al., 2006

In the paper

“When overexpressed, SGK1 reverses spatial memory impairments, as well as decrease the production and deposition of Aβ.”

What the sources say

• ?Not checked — no full text of the sourcecites Lian et al., 2020 source

In the paper

“In human AD patients, the level of SGK1 is not significantly different from age-matched controls. Still, there is a notable increase in the phosphorylation of N-myc downstream-regulated gene family member 1 (NDRG1), a specific target of SGK1”

What the sources say

• ?Not checked — no full text of the sourcecites Sahin et al., 2013 source

In the paper

“These studies underscore the pivotal role of SGK1 in the progression and pathophysiology of PD. However, the inconsistency in results can be attributed to factors such as the diversity of experimental models, dose-dependent effects, and variations in experimental methodologies.”

In the paper

“SGK1 is a potent antioxidant and has been implicated in the pathogenesis of HD”

What the sources say

• ?Not checked — no full text of the sourcecites Ferrelli et al., 2015 source
• ?Not checked — no full text of the sourcecites Rangone et al., 2004 source

In the paper

“Furthermore, upregulation of SGK1 elevates the levels of actin remodeling-related proteins, such as Rictor, Rac1, Cdc42, and Profilin-1 in the hippocampus of AD mice, which may impact the structure and function of neurons”

What the sources say

• ?Not checked — no full text of the sourcecites Chen et al., 2012 source
• ?Not checked — no full text of the sourcecites Lian et al., 2020 source

In the paper

“A recent study in an AD mouse model revealed significant myelin loss alongside increased oligodendrogenesis and remyelination, indicating concurrent myelin degeneration and repair during AD progression”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Chen et al., 2021a

In the paper

“Moreover, SGK phosphorylates huntingtin protein at serine 421, and this phosphorylation can protect striatal neurons from the toxicity of mutant huntingtin protein”

What the sources say

• ?Not checked — no full text of the sourcecites Rangone et al., 2004 source

In the paper

“Total SGK protein levels, encompassing both SGK1 and SGK3, show an upregulation trend in the brains of HD patients, with the concentration increasing as the severity of the disease progresses”

What the sources say

• ?Not checked — no full text of the sourcecites Rangone et al., 2004 source

In the paper

“MPTP treatment upregulates SGK1 and DRP1 expression dose-dependently, triggering neuronal damage via the SGK1-FOXO3a pathway and causing oxidative stress and mitochondrial dysfunction”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Li et al., 2019

In the paper

“In C2C12 cells, SGK1 was effectively reduced using siRNA, and the resulting inhibition of SGK1 led to an increased expression of α-syn, aligning with findings from the MPTP-treated mouse model”

What the sources say

• ?Not checked — no full text of the sourcecites Heo et al., 2023 source

In the paper

“Similarly, in the MPTP-induced PD mouse model, acupuncture stimulation maintained SGK1 expression at levels comparable to the control group, resulting in a reduction of α-synuclein levels”

What the sources say

• ?Not checked — no full text of the sourcecites Yeo and Lim, 2019 source

In the paper

“The increase in SGK1, through the inhibition of the GSK-3β/β-catenin pathway, ultimately suppresses caspase-3 activation, inhibiting neuronal apoptosis in TBI”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2013

In the paper

“Applying neuron-specific SGK1 knockdown ameliorated mitochondrial dysfunction, learning/memory, motor, and anxiety deficits following CA”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wu et al., 2024

In the paper

“Suggesting SGK1 aids in suppressing neuroinflammation in TBI by the GR signaling pathway and remyelination.”

In the paper

“In rats, SGK1 transcription levels are markedly induced in the neuron and oligodendrocyte area following cortical injury, with significant elevation observed by day three and sustained high expression levels for up to 14 days”

What the sources say

• ?Not checked — no full text of the sourcecites Imaizumi et al., 1994 source

In the paper

“Administering an SGK1 inhibitor 30 minutes before arterial occlusion in the brain similarly results in a significant reduction in infarct volume and improves NMDA currents and peak amplitudes in calcium-cultured neurons”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Inoue et al., 2016a

In the paper

“Pre-CA intraventricular injection of an SGK1 inhibitor in rats mitigated cortical hypoperfusion and neuroinflammation (evidenced by reduced Iba1 expression) following CA, and enhanced neuronal survival in the hippocampal CA1 region”

What the sources say

• ?Not checked — no full text of the sourcecites Lee et al., 2020 source

In the paper

“SGK1 mediates autophagy in mammals, and the loss of SGK1 function exacerbates mitochondrial permeability transition pore-dependent hepatic ischemia/reperfusion injury”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Zhou et al., 2019

In the paper

“In epileptic mice, activation of SGK1 leads to a decrease in pro-apoptotic Bim protein levels in the hippocampus, while anti-apoptotic protein Bcl-xL is upregulated”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Martin-Batista et al., 2021a

In the paper

“SGK1 in the brain regulates various ion channels, including those relevant to neurovascular coupling.”

In the paper

“The phenotype of SGK1 knockout mice is mild and only becomes pronounced under challenging conditions”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Lang et al., 2010b

In the paper

“The potential mechanisms of SGK1 in relation to neurological disorders, particularly its precise molecular targets and mechanisms, remain unclear.”

In the paper

“The complex role of SGK1 could also be one of the reasons for inconsistent results about SGK1 in neurological disorders.”

In the paper

“the research outcomes vary due to inconsistencies in the pathological models, intervention agents, and the timing of interventions, among other factors”

In the paper

“the role and targeting of SGK1 in various brain diseases studied, including neurodegenerative conditions, brain injuries, and psychiatric disorders, continue to be controversial.”

In the paper

“Regardless, SGK1 remains a viable target in the research of various brain disorders.”

In the paper

“whether SGK1 acts as a catalyst exacerbating DD symptoms or serves as a neuroprotective compensatory agent in DD remains unclear.”