Journal ArticleDOI
Role of Cell Cycle Re-Entry in Neurons: A Common Apoptotic Mechanism of Neuronal Cell Death
Jaume Folch,Felix Junyent,Ester Verdaguer,Carme Auladell,Javier G. Pizarro,Carlos Beas-Zarate,Mercè Pallàs,Antoni Camins +7 more
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TLDR
Given that cyclin-dependent kinase inhibitory drugs have neuroprotective and anti-apoptotic effects in experimental models, their potential application for the treatment of neurological disorders should be taken into account.Abstract:
Currently, there is no effective treatment for neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Thus, a major focus of neuroscience research is to examine the mechanisms involved in neuronal loss in order to identify potential drug targets. Recent results indicate that DNA damage and re-entry into the cell cycle may constitute a common pathway in apoptosis in neurological diseases. The role of the cell cycle in such disorders is supported by data on the brain of patients who showed an increase in cell-cycle protein expression. Indeed, studies performed in neuronal cell preparations indicate that oxidative stress could be the main mechanism responsible for cell cycle re-entry. DNA damage and repair after oxidative stress may activate the enzyme ataxia telangiectasia mutated, which is a cell-cycle regulator. Once the cell cycle is activated, the increase in the expression of transcription factor E2F-1 could induce neuronal apoptosis. Furthermore, the potential routes involved in E2F-1 induced apoptosis could be p53-dependent or p53-independent. Under this E2F-1 hypothesis of cell death, multiple mitochondria-dependent pathways may be activated, including caspase and caspase-independent signaling cascades. Finally, given that cyclin-dependent kinase inhibitory drugs have neuroprotective and anti-apoptotic effects in experimental models, their potential application for the treatment of neurological disorders should be taken into account.read more
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Ageing as a Risk Factor for Disease
Teresa Niccoli,Linda Partridge +1 more
TL;DR: Lowered activity of the nutrient-sensing insulin/insulin-like growth factor/Target of Rapamycin signalling network can extend healthy lifespan in yeast, multicellular invertebrates, mice and, possibly, humans.
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Neuronal Cell Death.
TL;DR: Which forms of cell death occur in stroke and Alzheimer's disease are reassess, and why it has been so difficult to pinpoint the type of neuronal death involved is discussed.
Journal ArticleDOI
Programmed cell death in aging.
TL;DR: Programmed cell death pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis and limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear.
Journal ArticleDOI
New Insights for Oxidative Stress and Diabetes Mellitus.
TL;DR: The mechanistic target of rapamycin, silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), and Wnt1 inducible signaling pathway protein 1 (WISP1) are especially justified to be considered treatment targets for DM.
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Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease
TL;DR: The bridging integrator 1 (BIN1) gene, also known as amphiphysin 2, has recently been identified as the most important risk locus for late onset Alzheimer's disease (LOAD), after apolipoprotein E (APOE).
References
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Journal ArticleDOI
Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration
Gentry N. Patrick,Lawrence R. Zukerberg,Margareta Nikolic,Margareta Nikolic,Suzanne M. de la Monte,Pieter Dikkes,Li-Huei Tsai,Li-Huei Tsai +7 more
TL;DR: It is found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease, and this accumulation correlates with an increase in Cdk5 kinase activity.
Journal ArticleDOI
G1 cell-cycle control and cancer
TL;DR: An increasingly complex and coherent view of G1 signalling networks, which coordinate cell growth, proliferation, stress management and survival, is helping to define the roots of malignancies and shows promise for the development of better cancer therapies.
Journal ArticleDOI
p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5
TL;DR: In this article, a regulatory subunit for cyclin-dependent kinase 5 (Cdk5) known as p35 was found to associate physically with Cdk5 in vivo.
Journal ArticleDOI
The E2F transcriptional network: old acquaintances with new faces.
TL;DR: How the discovery of new family members with unusual properties, the unexpected phenotypes of mutant animals, a diverse collection of biological activities, a large number of new putative target genes and the new modes of transcriptional regulation are described will shape a new and revised picture of the E2F transcriptional program.
Journal ArticleDOI
Apoptosis, autophagy, and more.
Richard A. Lockshin,Zahra Zakeri +1 more
TL;DR: Since switching among the alternative pathways to death is relatively common, interpretations based on knockouts or inhibitors, and therapies directed at controlling apoptosis must include these considerations.
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