MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau-phosphorylation, and apoptosis in postmitotic neurons.

摘要: 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 a specific miRNA, miR-26b, defined pathological areas human postmortem brains, starting from early stages AD (Braak III). Ectopic overexpression miR-26b rat primary postmitotic neurons led DNA replication and aberrant cell cycle entry (CCE) and, parallel, increased tau-phosphorylation, which culminated apoptotic death neurons. Similar tau hyperphosphorylation CCE typical features pre-AD brains. Sequence-specific inhibition culture is neuroprotective against oxidative stress. Retinoblastoma protein (Rb1), tumor suppressor, appears key direct target, mediates neuronal phenotypes. The downstream signaling involves upregulation Rb1/E2F pro-apoptotic transcriptional targets, including cyclin E1, corresponding downregulation inhibitor p27/Kip1. It further leads nuclear export activation Cdk5, kinase implicated phosphorylation, regulation cycle, Therefore, causes pleiotropic phenotypes that also AD. Elevated may thus contribute pathology.