Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease

Nagarsheth, Mehul H.; Viehman, Alex; Lippa, Sara M.; Lippa, Carol F.

doi:10.1016/j.jns.2006.01.007

Cited by 49 publications

(42 citation statements)

References 13 publications

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“…In contrast to the previous reports indicating a reduction in Notch activity in AD, two other studies showed a significant increase in Notch expression/activity in sporadic Alzheimer's disease (Berezovska et al, 1998;Nagarsheth et al, 2006). In addition, other neurodegenerative diseases such as Down syndrome (Fischer et al, 2005), Pick's (Nagarsheth et al, 2006) and Prion's disease (Ishikura et al, 2005), are characterized by concomitant increases in Notch expression and amyloid plaques formation.…”

Section: Notch In Alzheimer's Diseasementioning

confidence: 58%

“…In addition, other neurodegenerative diseases such as Down syndrome (Fischer et al, 2005), Pick's (Nagarsheth et al, 2006) and Prion's disease (Ishikura et al, 2005), are characterized by concomitant increases in Notch expression and amyloid plaques formation. It remains to be understood why progressive neurodegenerative diseases have different mechanisms in terms of Notch processing and signaling, and whether Notch effectively contributes to their pathobiology.…”

Section: Notch In Alzheimer's Diseasementioning

confidence: 99%

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Notch signaling in the brain: In good and bad times

Albèri

Hoey

Brai

et al. 2013

Ageing Research Reviews

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Section: Notch In Alzheimer's Diseasementioning

confidence: 58%

Section: Notch In Alzheimer's Diseasementioning

confidence: 99%

Notch signaling in the brain: In good and bad times

Albèri

Hoey

Brai

et al. 2013

Ageing Research Reviews

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“…9) Studies on Alzheimer's disease and Pick's disease demonstrated that with the onset of neurodegeneration in the adult brain, the Notch1 signaling pathway becomes activated as an attempt to compensate for neuronal loss and promote postmitotic neuronal growth. 10) Expression of Notch1-related molecules was found to change dynamically in postischemic neurogenic response.…”

mentioning

confidence: 99%

The Function of Notch1 Signaling Was Increased in Parallel with Neurogenesis in Rat Hippocampus after Chronic Fluoxetine Administration

Sui

Zhang

Guo

et al. 2009

Biological & Pharmaceutical Bulletin

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Chronic fluoxetine administration can increase neurogenesis in the adult hippocampus, but the molecular mechanisms remain unclear. The Notch1 signaling pathway is expressed highly in the hippocampus and could be a target for diverse environmental modulators of adult neurogenesis. This prompted us to investigate whether the effect of fluoxetine on hippocampal neurogenesis involves Notch1 signaling. In this study, the function of Notch1 signaling was investigated by real time polymerase chain reaction (PCR) and Western blot at different time points (14 d or 28 d) after fluoxetine administration. Simultaneously, hippocampal neurogenesis was determined by assessing cell proliferation, survival and differentiation. mRNA and protein expression of Notch1 signaling components (including Jag1, NICD, Hes1 and Hes5) in the hippocampus increased after fluoxetine administration, accompanied by cell proliferation and survival. These results indicate that chronic fluoxetine administration activates Notch1 signaling in the hippocampus, and the up-regulation of the Notch1 pathway brought about by chronic fluoxetine administration might partly contribute to increased neurogenesis in hippocampus. The findings may provide new insights into the regulatory mechanisms of neurogenesis induced by fluoxetine.

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“…In addition, increased Notch1 expression and amyloid plaques formation were observed in other neurodegenerative diseases such as Down syndrome (Fischer et al 2005), Pick's disease (Nagarsheth et al 2006) and Pion's disease (Ishikura et al 2005). Other evidence further demonstrates that Notch1 and Notch2 directly bind to APP in rat E18 neurons and human embryonic kidney (HEK) 293 cells (Chen et al 2006;Oh et al 2005;Oh et al 2010 (Roncarati et al 2002).…”

Section: Notch Signaling In Alzheimer's Diseasementioning

confidence: 98%

“…It was found that Notch1 expression and activity are increased in sporadic Alzheimer's disease (Berezovska et al 1998;Nagarsheth et al 2006). In addition, increased Notch1 expression and amyloid plaques formation were observed in other neurodegenerative diseases such as Down syndrome (Fischer et al 2005), Pick's disease (Nagarsheth et al 2006) and Pion's disease (Ishikura et al 2005).…”

Section: Notch Signaling In Alzheimer's Diseasementioning

confidence: 99%

Molecular mechanisms of Notch1-mediated neuronal cell death in ischemic stroke

Cheng¹

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Stroke is a devastating neurological disease with high mortality rate and has profound implications for health economics and resources globally. There is a sense of urgency for scientists to discover a pharmacological target in stroke that could modulate multiple molecular cell injury mechanisms since many therapeutic agents that targeted only a single injury mechanism result in disappointing outcomes in human clinical trials. During stroke, cerebral ischemia triggers a number of membrane bound receptor-mediated signaling cascades that can activate many downstream kinases and transcription factors known to induce neuronal apoptosis. The activation of the membrane receptor Notch1 and its signaling pathway is seen in the infarcted brain, which is shown to deteriorate the outcome of ischemic stroke.Notch1 is a transmembrane receptor that regulates cell fate decisions in the developing nervous system and adult brain. Binding of Notch's ligands leads to the proteolytic cleavage of Notch1 by γ-secretase and the generation of Notch1 intracellular domain (NICD1), which is able to translocate to the nucleus and regulate transcription of its downstream genes. Although Notch1 has been demonstrated to worsen stroke outcome by stimulating the infiltration of pro-inflammatory leukocytes and microglia-induced inflammatory responses, the molecular mechanisms of Notch1 in neurons following ischemic stroke in the induction of pro-apoptotic cascades are still not yet fully established.The present studies aim to investigate the role of γ-secretase-mediated Notch signaling pathway in the induction of neuronal cell death through its modulation with the nuclear factor-κB (NF-κB) pathway, the collaboration with hypoxia-inducible factor-1α (HIF-1α) pathway, and its contribution to the mitogen activated protein kinase (MAPK) pathway, which are all crucial in the induction of neuronal apoptosis. It also aims to observe the modulation of the pro-apoptotic proteins that are activated as a result of Notch1 activation in neurons following ischemic stroke.The present studies demonstrate that the inhibition of Notch1 activation using γ-secretase inhibitors protect neuronal cells against ischemia-induced cell death by targeting an apoptotic marker, cleaved caspase-3, NF-κB subunits p65, p50 and pro-apoptotic BH3-only protein, Bcl-2 interacting mediator of cell death (Bim). In addition, treatment of mice with the γ-secretase inhibitor reduces NICD1, phosphorylated-p65 and Bim expression levels, with reduced infarct size and improved functional outcome in a mouse model of focal ischemic stroke. These findings II suggest that γ-secretase-mediated Notch signaling endangers neurons after ischemic stroke by modulating the NF-κB-Bim pathway.Additional findings suggest that the HIF-1α pathway, a global regulation pathway of cellular response to hypoxia, is able to interact with Notch1 and modulate its signaling during ischemic stroke. Treatment with either a HIF-1α inhibitor or a γ-secretase inhibitor protects neurons against ischemic stress and...

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Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease

Cited by 49 publications

References 13 publications

Notch signaling in the brain: In good and bad times

Notch signaling in the brain: In good and bad times

The Function of Notch1 Signaling Was Increased in Parallel with Neurogenesis in Rat Hippocampus after Chronic Fluoxetine Administration

Molecular mechanisms of Notch1-mediated neuronal cell death in ischemic stroke

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