Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease

In the paper

“reactive oxygen species (ROS), which attack DNA to form oxidized bases and abasic sites”

What the sources say

• Not checked yetcites Lindahl & Barnes, 2000 source
• Partly supported

  The cellular DNA damage response section says ROS generate oxidative base modifications, supporting the oxidized-bases part. It does not say ROS attack DNA to form abasic sites; it describes DNA glycosylases excising modified bases during repair. No page number is available in our copy. (LLM, conf=0.86)

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

  In “Stochastic Errors in DNA Replication or Spontaneous Deamination as a Source of Mutation” (page not provided), the paper identifies 8-oxoguanine as a DNA lesion arising from reactive oxygen, supporting the oxidized-bases portion. The passages found do not say that ROS form abasic sites. (LLM, conf=0.85)

  cites Tubbs & Nussenzweig, 2017 sourceExperimental — accuracy not yet measured

In the paper

“In many cases, DNA damage seems to be one of the earliest indicators of neuropathology”

What the sources say

• Not checked yetcites Chow & Herrup, 2015 source
• ?Not matched

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

  cites Simpson et al, 2015, 2016
• Partly supported

  The Results report DNA double-strand breaks in mild cognitive impairment as well as Alzheimer’s disease, and the Discussion describes their accumulation at relatively early stages of the illness (page not provided). This supports an early association in Alzheimer’s disease, but the paper does not establish DNA damage as one of the earliest indicators of neuropathology across many conditions. (LLM, conf=0.84)

  cites Shanbhag et al, 2019 sourceExperimental — accuracy not yet measured

In the paper

“Increased PARP1 activation and elevated poly(ADP‐ribose) has been observed in numerous neurodegenerative disorders and their associated animal models (Thapa et al, 2021; Mao & Zhang 2022).”

What the sources say

• Not checked yetcites Thapa et al, 2021 source
• Supported

  The “PARP1 and neurodegenerative diseases” section reports excessive PARP1 activation in several disorders, including Huntington’s disease, ALS and multiple sclerosis, and increased PARylation in ataxia-telangiectasia mouse and worm models. The Alzheimer’s and Parkinson’s disease sections also describe PARP1 activation, supporting the broad paraphrase. (LLM, conf=0.87)

  cites Mao & Zhang 2022 source

In the paper

“To this end, genome‐wide profiling of DNA breaks in post‐mitotic neurons have revealed that their locations are likely major mediators of their toxicity.”

What the sources say

• Partly supported

  The paper’s Repair-seq results (section labeled Abstract; page unavailable) map genome-wide DNA repair hotspots in postmitotic human neurons and suggest that hotspots protect essential genomic elements. It profiles repair synthesis rather than DNA breaks themselves, and it does not establish that break locations are major mediators of toxicity. (LLM, conf=0.88)

  cites Reid et al, 2021 sourceExperimental — accuracy not yet measured
• Not checked yetcites Wu et al, 2021

In the paper

“These data suggest that on top of its function as a pro‐survival and pro‐inflammatory transcription factor, NF‐kB is also critical for homeostatic neuronal function (Kaltschmidt & Kaltschmidt, 2009).”

What the sources say

• Supported

  The NEURONS section (page unavailable) describes constitutive NF-kB activity associated with physiological basal synaptic transmission. The LEARNING AND MEMORY section (page unavailable) reports impaired learning, synaptic plasticity, and synapse formation when neuronal NF-kB is inhibited or ablated. Together, these support its importance for normal neuronal function. (LLM, conf=0.88)

  cites Kaltschmidt & Kaltschmidt, 2009 source

In the paper

“a wealth of evidence indicates deficient DNA damage repair underlies many neurological disorders, especially age‐associated neurodegenerative diseases.”

What the sources say

• Not checked yetcites Hoeijmakers, 2009 source
• Not checked yetcites Madabhushi et al, 2014 source
• Not checked yetcites Chow & Herrup, 2015 source

In the paper

“work establishing a role for senescence in the aging and diseased brain reveals DNA damage may play a central role in neuroinflammation associated with neurodegenerative disease.”

What the sources say

• Not checked yetcites Bussian et al, 2018 source
• Not checked yetcites Musi et al, 2018 source
• Not checked yetcites Chow et al, 2019 source

In the paper

“These insults ultimately push cellular fate toward apoptosis, senescence, or uncontrolled cell division”

What the sources say

• Not checked yetcites Hoeijmakers, 2009 source
• Not checked yetcites Madabhushi et al, 2014 source
• Not checked yetcites Chow & Herrup, 2015 source

In the paper

“the majority ultimately manifest in the form of single‐strand breaks (SSBs)”

What the sources say

• Not checked yetcites Lindahl & Barnes, 2000 source
• Not checked yetcites Madabhushi et al, 2014 source
• Not checked yetcites Tubbs & Nussenzweig, 2017 source

In the paper

“we are just beginning to appreciate the significance of a lesion’s genomic location in relation to its effect on neuronal activity and, ultimately, degeneration”

What the sources say

• ?Not matched

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

  cites Lodato et al, 2015, 2018
• Not checked yetcites Wei et al, 2016 source
• Not checked yetcites Reid et al, 2021 source

In the paper

“neurons exhibit substantial mitochondrial respiration, consuming approximately 20% of the body’s available oxygen”

What the sources say

• Not checked yetcites Attwell & Laughlin, 2001 source

In the paper

“suggesting it may be an initiating lesion of toxicity”

In the paper

“postmitotic neurons presumably incur the majority of their DSBs through transcriptional activity”

In the paper

“A well‐established link exists between DNA damage and neurodegenerative diseases.”

What the sources say

• Not checked yetcites Chow & Herrup, 2015 source
• ?Not matched

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

  cites Simpson et al, 2015, 2016
• Not checked yetcites Shanbhag et al, 2019 source

In the paper

“ROS‐mediated DNA damage is greatest in the nervous system”

What the sources say

• Not checked yetcites Nakamura & Swenberg, 1999

In the paper

“The nervous system is particularly sensitive to loss‐of‐function mutations in DNA repair proteins.”

In the paper

“while DNA breaks may serve a physiological function in learning and memory, their recurrence in neuron regulatory sequences makes these regions extremely vulnerable to mutation and translocation.”

In the paper

“Combined, these features reduce the burden of DNA damage toxicity in glia.”

In the paper

“Even simply introducing a mouse to a new environment is quickly followed by the induction of DSBs in neurons”

What the sources say

• ?Not matched

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

  cites Suberbielle et al, 2013, 2015

In the paper

“work has shown that some may underly neurodevelopmental and neurodegenerative disease.”

What the sources say

• ?Not matched

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

  cites Wei et al, 2016, 2018
• Not checked yetcites Wang et al, 2020 source
• Not checked yetcites Park et al, 2019 source

In the paper

“the protein kinase ATM phosphorylates numerous downstream substrates such as histone variant H2A.X, checkpoint kinase 2 (CHK2), and p53 to initiate DSB repair, cell cycle arrest, and apoptosis, respectively.”

In the paper

“DNA repair mapping reveals that postmitotic neurons do indeed accumulate breaks in regulatory elements associated with neuronal function”

What the sources say

• Not checked yetcites Reid et al, 2021 source
• Not checked yetcites Wu et al, 2021

In the paper

“somatic mutations induced by erroneous DNA damage repair or transposable elements are a common feature of neural development, giving rise to neuron diversity through genomic mosaicism”

What the sources say

• Not checked yetcites McConnell et al, 2013 source
• Not checked yetcites Alt & Schwer, 2018 source
• Not checked yetcites Lodato & Walsh, 2019 source

In the paper

“mutations in TDP2 result in a rare neurological disease termed spinocerebellar ataxia autosomal recessive 23 (SCAR23)”

What the sources say

• Not checked yetcites Zagnoli‐Vieira et al, 2018
• Not checked yetcites Gómez‐Herreros et al, 2014: 2
• Not checked yetcites Errichiello et al, 2020 source

In the paper

“a DSB‐mapping technique known as END‐seq was recently used to identify strand breaks in human induced pluripotent stem cell (iPSC)‐derived neurons, resulting in the finding that enhancers are hotspots for SSBs”

What the sources say

• Not checked yetcites Canela et al, 2016 source
• Not checked yetcites Wu et al, 2021

In the paper

“The explanation for this sensitivity may lie in the hallmarks of neuronal identity. That is, neurons perform transcriptionally and energetically demanding cellular functions and are post‐mitotic and long‐lived.”

In the paper

“Because HR requires sister chromatids, this pathway can only occur in cycling cells during or following S phase.”

In the paper

“DNA breaks seem to serve a functional role in neuronal activity”

What the sources say

• Not checked yetcites Madabhushi et al, 2015 source
• Not checked yetcites Stott et al, 2021 source
• ?Not matched

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

  cites Suberbielle et al, 2013, 2015

In the paper

“Notably, CAG expansion has been found to be dependent upon DNA repair proteins such as OGG1, MLH1, and MSH2, whose detection of oxidized or mismatched bases in these repetitive elements could potentially elicit erroneous repair, leading to CAG expansion (Kovtun et al, 2007; Bettencourt et al, 2016; Pinto et al, 2013; Manley et al, 1999; Lee et al, 2017, 1).”

What the sources say

• Not checked yetcites Kovtun et al, 2007 source
• Not checked yetcites Bettencourt et al, 2016 source
• Not checked yetcites Pinto et al, 2013 source

In the paper

“the pathogenic load of a loss‐of‐function mutation accelerates the development of age‐associated pathology”

In the paper

“To date, loss‐of‐function mutations in SSBR proteins have manifested exclusively as neurodegenerative syndromes.”

In the paper

“oxidative damage‐induced poly(ADP‐ribose) mediates α‐synuclein aggregation and consequent neurodegeneration in PD (Kam et al, 2018)”

What the sources say

• Not checked yetcites Kam et al, 2018 source

In the paper

“With the exception of AOA5, which seems to have manifested exclusively in adults so far (Hoch et al, 2017: 1; O’Connor et al, 2018: 1), the majority of DNA damage disorders typically present in early childhood.”

What the sources say

• Not checked yetcites Hoch et al, 2017: 1 source
• Not checked yetcites O’Connor et al, 2018: 1 source

In the paper

“Defective XRCC1 manifests in individuals as Ataxia with Oculomotor apraxia Type 5 (AOA5), another slow‐progressing neurodegenerative disease.”

What the sources say

• Not checked yetcites Hoch et al, 2017 source
• Not checked yetcites O’Connor et al, 2018: 1 source

In the paper

“Gene‐wide association studies have further identified SNPs in DNA maintenance genes that influence the age of onset in this disease (Lee et al, 2015; Moss et al, 2017).”

What the sources say

• Not checked yetcites Lee et al, 2015 source
• Not checked yetcites Moss et al, 2017 source

In the paper

“whether the resulting pathologies of a DNA repair deficit are developmental or age‐associated likely depends on both the brain cell type composition at the time and the selective vulnerabilities of different neuronal subtypes to different repair deficits.”

In the paper

“facilitates the formation of cytoplasmic TDP‐43 foci in ALS (McGurk et al, 2018a, 2018b)”

What the sources say

• Not checked yetcites McGurk et al, 2018a, 2018b

In the paper

“Deficient DNA damage repair in these vulnerable NPCs results in developmental abnormalities such as microcephaly”

In the paper

“inheritable DNA damage disorders, which frequently present with neurologic abnormalities”

In the paper

“Aberrant DNA repair may also directly mediate the severity of neurodegenerative disorders like HD, whose toxicity is derived from the CAG trinucleotide expansion of the Huntingtin gene.”

In the paper

“Similarly, DSB marker proteins correlate with cognitive impairment in individuals with low levels of amyloid and tau pathology (Simpson et al, 2015).”

What the sources say

• Not checked yetcites Simpson et al, 2015 source

In the paper

“it is likely that post‐mitotic neurons are bearing the brunt of the DNA repair deficit.”

In the paper

“Therefore, erroneous DNA repair mechanisms also directly influence HD severity.”

In the paper

“many DNA damage disorders are also defined by age‐associated pathologies such as progressive brain atrophy and peripheral neuropathy.”

In the paper

“we must acknowledge the pivotal role of DNA damage repair in neurodevelopment”

In the paper

“Specifically, increased DDR foci are observed in neurons from individuals with mild cognitive impairment (MCI) and AD compared to aged counterparts (Shanbhag et al, 2019).”

What the sources say

• Not checked yetcites Shanbhag et al, 2019 source

In the paper

“Accumulation of SNVs at neurodegeneration risk genes could potentially increase risk of disease development.”

In the paper

“an individual devoid of DNA repair mutations must experience the progressive stress of aging (i.e. damage accumulation, oxidative stress, declining DNA repair enzyme efficiency) in order to recapitulate the pathogenic load of a DNA damage disorder.”

In the paper

“and FUS activates and recruits the XRCC1‐LIG3 complex to sites of oxidative DNA damage in a PARP1‐dependent manner (Naumann et al, 2018; Wang et al, 2018a).”

What the sources say

• Not checked yetcites Naumann et al, 2018 source
• Not checked yetcites Wang et al, 2018a

In the paper

“However, toxic aggregation of α‐synuclein in the nucleus or cytosol elicits the accumulation of DSBs (Vasquez et al, 2017; Milanese et al, 2018).”

What the sources say

• Not checked yetcites Vasquez et al, 2017 source
• Not checked yetcites Milanese et al, 2018 source

In the paper

“can mediate neuroinflammatory activity in AD (Kauppinen et al, 2011)”

What the sources say

• Not checked yetcites Kauppinen et al, 2011 source

In the paper

“Tau may also play a role in DSB repair as well, as its deletion in the mouse brain leads to the accumulation of DSB foci in neurons (Violet et al, 2014; Mansuroglu et al, 2016).”

What the sources say

• Not checked yetcites Violet et al, 2014 source
• Not checked yetcites Mansuroglu et al, 2016 source

In the paper

“Importantly, removal of senescent cells promotes healthy aging in mice, making senescence‐associated inflammatory signaling an attractive target of therapeutic intervention for aging and age‐related disease (Tilstra et al, 2012; Childs et al, 2015; Baker et al, 2016; Ogrodnik et al, 2021).”

What the sources say

• Not checked yetcites Tilstra et al, 2012 source
• Not checked yetcites Childs et al, 2015 source
• Not checked yetcites Baker et al, 2016 source

In the paper

“Indeed, many of the risk genes associated with AD mediate their effects through microglia, the brain‐resident macrophages (Glass et al, 2010; Heneka et al, 2015; Nott et al, 2019).”

What the sources say

• Not checked yetcites Glass et al, 2010 source
• Not checked yetcites Heneka et al, 2015 source
• Not checked yetcites Nott et al, 2019 source

In the paper

“Initially, induction of persistent DDR signaling in cell cultures including fibroblasts (Coppé et al, 2008; Rodier et al, 2009), bone marrow‐derived macrophages (BMDMs) (Härtlova et al, 2015), and primary monocytes (Brzostek‐Racine et al, 2011) was found to elicit the SASP (Coppé et al, 2008).”

What the sources say

• Not checked yetcites Coppé et al, 2008 source
• Not checked yetcites Rodier et al, 2009 source
• Not checked yetcites Härtlova et al, 2015 source

In the paper

“FUS is an RNA/DNA binding protein that has been found to facilitate DSB repair through its colocalization with HDAC1 (Wy et al, 2013, 1).”

What the sources say

• Not checked yetcites Wy et al, 2013, 1

In the paper

“Furthermore, phosphorylation of FUS occurs in response to DSB detection by proteins ATM and DNA‐PK (Gardiner et al, 2008; Deng et al, 2014)”

What the sources say

• Not checked yetcites Gardiner et al, 2008 source
• Not checked yetcites Deng et al, 2014 source

In the paper

“It follows that while these breaks may be functionally relevant, over time, their erroneous repair could lead to disruptive translocations, mutations, and genomic instability.”

In the paper

“This secretory profile was found to be at least partially ATM‐dependent, implying the importance of DSB repair specifically in immune activation (Rodier et al, 2009; Brzostek‐Racine et al, 2011).”

What the sources say

• Not checked yetcites Rodier et al, 2009 source
• Not checked yetcites Brzostek‐Racine et al, 2011

In the paper

“Thus, senescence is now considered as a potential driver of neuroinflammation and neurodegeneration.”

In the paper

“Previous work with AT fibroblasts had shown that the canonical immune transcription factor NF‐kB is activated in an ATM‐dependent manner following treatment with a radiomimetic, ionizing radiation, or topoisomerase inhibitor (Lee et al, 1998; Piret et al, 1999; Li et al, 2001).”

What the sources say

• Not checked yetcites Lee et al, 1998 source
• Not checked yetcites Piret et al, 1999 source
• Not checked yetcites Li et al, 2001

In the paper

“In addition to PARP1 activity, many genes that encode the building blocks of neurodegenerative proteinopathies have been found to play a role in DDR as well.”

In the paper

“While these findings have firmly established DNA breaks as a mechanism of neurodegenerative disease, the mechanisms by which break location may contribute to disease progression are not well described.”

In the paper

“In addition to DNA damage, neuroinflammation has emerged as a core feature and mechanism of neurodegenerative disease.”

In the paper

“Recently, TDP‐43 was also found to be directly involved in NHEJ through its recruitment and stabilization of the XRCC4‐LIG4 complex at DSBs (Guerrero et al, 2019; Mitra et al, 2019).”

What the sources say

• Not checked yetcites Guerrero et al, 2019 source
• Not checked yetcites Mitra et al, 2019 source

In the paper

“As described earlier, the use of nucleoside analog incorporation to map DNA repair has led to the observation that postmitotic neurons harbor SSBs and other forms of breaks in the regulatory regions of genes that modulate synaptic plasticity and neuronal function (Reid et al, 2021; Wu et al, 2021).”

What the sources say

• Not checked yetcites Reid et al, 2021 source
• Not checked yetcites Wu et al, 2021

In the paper

“Nevertheless, observations of senescent‐like phenotypes in neurons have been reported for quite some time.”

What the sources say

• Not checked yetcites Jurk et al, 2012 source

In the paper

“An additional mechanism of cytosolic DNA‐mediated inflammation is through the NLRP3 inflammasome, which senses cell stressors (such as cytosolic DNA) to activate the cleavage of pro‐1L1b and pro‐IL18 via Caspase I to elicit their secretion.”

In the paper

“Additionally, senescent astrocytes have been identified as modulators of PD pathology (Chinta et al, 2018).”

What the sources say

• Not checked yetcites Chinta et al, 2018 source

In the paper

“Here, DSBs were considered the major driver of these senescence‐associated phenotypes because knock‐out of p21, a protein activated by p53 to initiate DSB‐induced cell cycle arrest, was able to mitigate their enrichment.”

What the sources say

• Not checked yetcites Jurk et al, 2012 source

In the paper

“AGS is caused by mutations in genes that regulate nucleic acid metabolism.”

What the sources say

• Not checked yetcites Crow & Manel, 2015 source

In the paper

“Interestingly, sequencing the cytosolic DNA fragments from these microglia revealed that most were derived from the nuclear DNA as intergenic repetitive elements, suggesting that the source of cytosolic DNA may not be random (Song et al, 2021).”

What the sources say

• Not checked yetcites Song et al, 2021 source

In the paper

“Thus, the interplay between NF‐kB and p53 strongly influence cellular fate following DNA damage accumulation (Karin & Lin, 2002).”

What the sources say

• Not checked yetcites Karin & Lin, 2002 source

In the paper

“Subsequent studies confirmed that following DSB induction, activated ATM couples with a number of protein intermediates leading to its cytoplasmic transport and downstream activation of NF‐kB (Hinz et al, 2010; Wu et al, 2010; Miyamoto, 2011).”

What the sources say

• Not checked yetcites Hinz et al, 2010 source
• Not checked yetcites Wu et al, 2010
• Not checked yetcites Miyamoto, 2011 source

In the paper

“In particular, microglial NLRP3 has been shown to be a major driver of amyloid beta and tau toxicity in AD, suggesting its activation has important implications for disease progression (Halle et al, 2008; Venegas et al, 2017; Ising et al, 2019).”

What the sources say

• Not checked yetcites Halle et al, 2008 source
• Not checked yetcites Venegas et al, 2017 source
• Not checked yetcites Ising et al, 2019 source

In the paper

“Finally, removal of senescent microglia from aged mice has been found to improve cognition (Ogrodnik et al, 2021).”

What the sources say

• Not checked yetcites Ogrodnik et al, 2021

In the paper

“Because DNA damage accumulates in neurons early on in AD, and because it is also a primary driver of senescence, it is worth hypothesizing that DNA lesions mediate neurodegeneration at least in part through neuronal senescence, although senescence in other cell types clearly also plays important roles in neurodegeneration.”

In the paper

“This dataset was later re‐analyzed to show that neurons with high levels of tau were enriched for signatures of DNA damage and senescence (Dunckley et al, 2006; Musi et al, 2018).”

What the sources say

• Not checked yetcites Dunckley et al, 2006 source
• Not checked yetcites Musi et al, 2018 source

In the paper

“For example, ATM‐deficient microglia have been shown to accumulate cytosolic DNA, thus activating the cGAS‐STING pathway to elicit pro‐inflammatory and neurotoxic signals (Quek et al, 2017; Song et al, 2019).”

What the sources say

• Not checked yetcites Quek et al, 2017
• Not checked yetcites Song et al, 2019 source

In the paper

“As early as 2012, the term “senescence” was used to describe pathological features of neurons in the aged mouse brain, including increased DSBs, lipid peroxidation, and senescent‐associated β‐galactosidase staining (Jurk et al, 2012).”

What the sources say

• Not checked yetcites Jurk et al, 2012 source

In the paper

“Accordingly, RNASEH2 murine models of AGS reveal that CGAS‐STING sensing of micronuclei is the cause for type I IFN signaling in this disease (Mackenzie et al, 2016, 2017; Pokatayev et al, 2016).”

What the sources say

• ?Not matched

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

  cites Mackenzie et al, 2016, 2017
• Not checked yetcites Pokatayev et al, 2016 source

In the paper

“Senescent‐like phenotypes in neurons have also been noted in other models of aging and neurodegeneration (Chow et al, 2019; Moreno‐Blas et al, 2019).”

What the sources say

• Not checked yetcites Chow et al, 2019 source
• Not checked yetcites Moreno‐Blas et al, 2019

In the paper

“For example, deficits in RNASEH2, an enzyme responsible for removing ribonucleotides from DNA and resolving R‐loops, comprise more than half of AGS diagnoses (Crow & Manel, 2015).”

What the sources say

• Not checked yetcites Crow & Manel, 2015 source

In the paper

“Recent single‐nucleus RNA sequencing of AT cerebella reveals that microglial activation likely precedes neuronal degeneration, further emphasizing the role of microglia in ATM‐mediated neuropathology (Lai et al, 2021).”

What the sources say

• Not checked yetcites Lai et al, 2021

In the paper

“Thus, dysregulated NF‐kB signaling in neurons could be a key mechanism linking DNA damage accumulation, altered synaptic function, and disease progression.”

In the paper

“While these are mechanisms specific to neurons, emerging evidence also suggests that many cell types in the brain, including astrocytes, microglia, oligodendrocytes, and neurons, may mediate the cytotoxicity of DNA damage through senescence‐associated signaling.”

In the paper

“Indeed, observations of neuron‐derived immune signaling at early stages of neurodegenerative disease indicate that this may play a role in disease progression (Dutta et al, 2020; Welikovitch et al, 2020).”

What the sources say

• Not checked yetcites Dutta et al, 2020 source
• Not checked yetcites Welikovitch et al, 2020 source

In the paper

“Intriguingly, the inflammatory transcription factor NF‐kB also plays neuron‐specific roles in learning and memory.”

What the sources say

• Not checked yetcites O’Mahony et al, 2006 source
• Not checked yetcites Boersma et al, 2011 source

In the paper

“The utilization of murine models of DNA damage and DNA break mapping techniques have allowed us to identify how DNA damage may regulate the expression of genes essential for neuronal function, and how this might lead to dysfunction later in life.”

In the paper

“Inhibition of NF‐kB signaling specifically in neurons impairs synaptic plasticity and synaptogenesis (O’Mahony et al, 2006; Boersma et al, 2011).”

What the sources say

• Not checked yetcites O’Mahony et al, 2006 source
• Not checked yetcites Boersma et al, 2011 source

In the paper

“However, work examining the immune response to neurotropic viral infections reveals neuron‐derived inflammatory signaling is a critical feature of the antiviral response (Klein et al, 2005; Chakraborty et al, 2010; Di Liberto et al, 2018).”

What the sources say

• Not checked yetcites Klein et al, 2005 source
• Not checked yetcites Chakraborty et al, 2010 source
• Not checked yetcites Di Liberto et al, 2018 source

In the paper

“Furthermore, suppression of neuronal NF‐kB in vivo renders neurons more susceptible to kainic acid‐induced neurotoxicity (Fridmacher et al, 2003).”

What the sources say

• Not checked yetcites Fridmacher et al, 2003 source

In the paper

“Indeed, the protein machinery required to detect cytosolic DNA such as STING is reported to be low in neurons compared to glial cells (Mathur et al, 2017; Song et al, 2019).”

What the sources say

• Not checked yetcites Mathur et al, 2017 source
• Not checked yetcites Song et al, 2019 source

In the paper

“Regardless, it is clear that DNA damage can elicit neuron dysfunction broadly through two distinct mechanisms.”

In the paper

“First, the location of the lesion has a significant impact on transcriptional mechanisms required for normal cell function.”

In the paper

“Second, the downstream signaling pathways of lesion detection, whether they be through DDR or cytosolic nucleic acid sensing, can elicit apoptotic or inflammatory signaling that lead to neurotoxicity.”