Notch signaling and neuronal death in stroke

Arumugam, Thiruma V.; Baik, Sang‐Ha; Balaganapathy, Priyanka; Sobey, Christopher G.; Mattson, Mark P.; Jo, Dong Gyu

doi:10.1016/j.pneurobio.2018.03.002

Cited by 114 publications

(88 citation statements)

References 183 publications

(254 reference statements)

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“…In addition to the direct, genetic causal link of Notch dysfunction to CADASIL, Notch pathway modulation has been investigated in several paradigms of experimental stroke in rodents. The majority of studies suggest that Notch activation is beneficial in this context, notwithstanding the fact that Notch is a finely tuned molecule with a dynamic on-off state, constantly responding to spatiotemporal cues, thereby complicating the interpretation of these studies (Arumugam et al, 2018). In the aftermath of stroke, enhanced neural progenitor proliferation is accompanied by an upregulation of Notch activity and target gene expression (Chen et al, 2008;Kawai, Takagi, Nakahara, & Takeo, 2005;Wang, Mao, Xie, Greenberg, & Jin, 2009).…”

Section: Notch In Ischemia and Brain Injurymentioning

confidence: 99%

The Notch pathway in CNS homeostasis and neurodegeneration

Artavanis‐Tsakonas

Louvi

2019

WIREs Developmental Biology

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The role of the Notch signaling pathway in neural development has been well established over many years. More recent studies, however, have demonstrated that Notch continues to be expressed and active throughout adulthood in many areas of the central nervous system. Notch signals have been implicated in adult neurogenesis, memory formation, and synaptic plasticity in the adult organism, as well as linked to acute brain trauma and chronic neurodegenerative conditions. NOTCH3 mutations are responsible for the most common form of hereditary stroke, the progressive disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Notch has also been associated with several progressive neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Although numerous studies link Notch activity with CNS homeostasis and neurodegenerative diseases, the data thus far are primarily correlative, rather than functional. Nevertheless, the evidence for Notch pathway activity in specific neural cellular contexts is strong, and certainly intriguing, and points to the possibility that the pathway carries therapeutic promise. This article is categorized under: Nervous System Development > Flies Signaling Pathways > Cell Fate Signaling Nervous System Development > Vertebrates: General Principles

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Section: Notch In Ischemia and Brain Injurymentioning

confidence: 99%

The Notch pathway in CNS homeostasis and neurodegeneration

Artavanis‐Tsakonas

Louvi

2019

WIREs Developmental Biology

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“…Increasing evidence suggests that Notch signaling in cerebral ischemia is involved in inflammation, oxidative stress, apoptosis, angiogenesis, synaptic plasticity and the function of blood-brain barrier [26][27][28]. Not surprisingly, Notch2 is upregulated with increased cell death shortly after cerebral ischemia injury in hippocampal areas [27]. Meanwhile, a similar increase in Notch2 in apoptotic cells was found after oxygen glucose deprivation treatment [29].In addition, Notch2 signaling is associated with the progression of atherosclerosis [30].…”

Section: Discussionmentioning

confidence: 96%

“…In previous studies, PRR11 was considered to be a disadvantageous factor affecting the regulation of tumor cells, but its role and clinical application value in stroke are largely unknown [24,25]. Increasing evidence suggests that Notch signaling in cerebral ischemia is involved in inflammation, oxidative stress, apoptosis, angiogenesis, synaptic plasticity and the function of blood-brain barrier [26][27][28]. Not surprisingly, Notch2 is upregulated with increased cell death shortly after cerebral ischemia injury in hippocampal areas [27].…”

Section: Discussionmentioning

confidence: 99%

Hub genes of stroke identified by weighted gene co-expression network analysis

Zhai²,

et al. 2019

Preprint

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Background Microarray-based gene expression profiling has been widely used in biomedical research. Weighted gene co-expression network analysis (WGCNA) can link microarray data directly to clinical traits and to identify rules for predicting pathological stage and prognosis of disease, it has been found useful in many biological processes. Stroke is one of the most common diseases worldwide, yet molecular mechanisms of its pathogenesis are largely unknown. We aimed to construct gene co-expression networks to identify key modules and hub genes associated with the pathogenesis of stroke.Results In this study, we screened out the differentially expressed genes from gene microarray expression profiles, then constructed the free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify key modules and hub genes. Subsequently, functional enrichment and the receiver operating characteristic (ROC) curve analysis were performed. And the results show that a total of 11,747 most variant genes were used for co-expression network construction. Pink and yellow modules were found to be the most significantly related to stroke. Functional enrichment analysis showed that the pink module was mainly involved in regulation of neuron regeneration, and the repair of DNA damage, while the yellow module was mainly enriched in ion transport system dysfunction which were correlated with neuron death. A total of 8 hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) were identified and validated at transcriptional levels (other datasets) and by existing literatures.Conclusions Eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of stroke in the future.

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“…Previous studies report that PRR11 is implicated in tumor progression.However, the role and clinical application value of PRR11 in stroke is unknown [36,37]. Studies show that Notch signaling in cerebral ischemia plays a role in in ammation, oxidative stress, apoptosis, angiogenesis, synaptic plasticity and the function of blood-brain barrier [38][39][40]. Notably, Notch2 is upregulated with increased cell death shortly after cerebral ischemia injury in hippocampal areas [39].…”

Section: Discussionmentioning

confidence: 99%

“…Studies show that Notch signaling in cerebral ischemia plays a role in in ammation, oxidative stress, apoptosis, angiogenesis, synaptic plasticity and the function of blood-brain barrier [38][39][40]. Notably, Notch2 is upregulated with increased cell death shortly after cerebral ischemia injury in hippocampal areas [39]. Further, an increase in Notch2 levels in apoptotic cells was reported after oxygen and glucose deprivation treatment [41].In addition, Notch2 signaling is associated with the progression of atherosclerosis [42].…”

Section: Discussionmentioning

confidence: 99%

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

Zhai

et al. 2020

Preprint

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BACKGROUD: Microarray-based gene expression profiling is widely used in biomedical research. Weighted gene co-expression network analysis (WGCNA) links microarray data directly to clinical traits and identifies rules for predicting pathological stage and prognosis of disease.WGCNA is useful in understandingmany biological processes. Stroke is a common disease worldwide, however, molecular mechanisms of its pathogenesis are largely unknown. The aim of this study was to construct gene co-expression networks for identification of key modules and hub genes associated with stroke pathogenesis.METHODS: Gene microarray expression profiles of stroke samples were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by the limma package in R software. WGCNA was used to construct free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify key modules and hub genes. Subsequently, functional enrichment analyses were performed. Further, receiver operating characteristic (ROC) curve analysis was carried out to validate expression of hub genes and literature validation was performed as well.RESULTS: A total of 11,747 most variant genes were used for co-expression network construction. Pink and yellow modules were significantly correlated to stroke pathogenesis. Functional enrichment analysis showed that the pink module was mainly involved in regulation of neuron regeneration, and repair of DNA damage.On the other hand, yellow module was mainly enriched in ion transport system dysfunction which was correlated with neuron death. A total of eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) were identified and validated at transcriptional levels and through existing literature.CONCLUSION: The eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) identified in the study are potentialbiomarkers and therapeutic targets for effective diagnosis and treatment of stroke.

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Notch signaling and neuronal death in stroke

Cited by 114 publications

References 183 publications

The Notch pathway in CNS homeostasis and neurodegeneration

The Notch pathway in CNS homeostasis and neurodegeneration

Hub genes of stroke identified by weighted gene co-expression network analysis

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

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