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- W2005202312 abstract "MicroRNA (miRNA) functions in the pathogenesis of major neurodegenerative diseases such as Alzheimer's disease (AD) are only beginning to emerge. We have observed significantly elevated levels of a specific miRNA, miR-26b, in the defined pathological areas of human postmortem brains, starting from early stages of AD (Braak III). Ectopic overexpression of miR-26b in rat primary postmitotic neurons led to the DNA replication and aberrant cell cycle entry (CCE) and, in parallel, increased tau-phosphorylation, which culminated in the apoptotic cell death of neurons. Similar tau hyperphosphorylation and CCE are typical features of neurons in pre-AD brains. Sequence-specific inhibition of miR-26b in culture is neuroprotective against oxidative stress. Retinoblastoma protein (Rb1), a major tumor suppressor, appears as the key direct miR-26b target, which mediates the observed neuronal phenotypes. The downstream signaling involves upregulation of Rb1/E2F cell cycle and pro-apoptotic transcriptional targets, including cyclin E1, and corresponding downregulation of cell cycle inhibitor p27/Kip1. It further leads to nuclear export and activation of Cdk5, a major kinase implicated in tau phosphorylation, regulation of cell cycle, and death in postmitotic neurons. Therefore, upregulation of miR-26b in neurons causes pleiotropic phenotypes that are also observed in AD. Elevated levels of miR-26b may thus contribute to the AD neuronal pathology." @default.
- W2005202312 created "2016-06-24" @default.
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- W2005202312 creator A5029594341 @default.
- W2005202312 creator A5040552656 @default.
- W2005202312 creator A5088110750 @default.
- W2005202312 date "2013-09-11" @default.
- W2005202312 modified "2023-10-02" @default.
- W2005202312 title "MiR-26b, Upregulated in Alzheimer's Disease, Activates Cell Cycle Entry, Tau-Phosphorylation, and Apoptosis in Postmitotic Neurons" @default.
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- W2005202312 doi "https://doi.org/10.1523/jneurosci.1327-13.2013" @default.
- W2005202312 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3810537" @default.
- W2005202312 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24027266" @default.
- W2005202312 hasPublicationYear "2013" @default.
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