%0 Journal Article %A Rachid El Fatimy %A Shaomin Li %A Zhicheng Chen %A Tasnim Mushannen %A Sree Gongala %A Zhiyun Wei %A Darrick T. Balu %A Rosalia Rabinovsky %A Adam Cantlon %A Abdallah Elkhal %A Dennis J. Selkoe %A Kai C. Sonntag %A Dominic M. Walsh %A Anna M. Krichevsky %T MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways %D 2018 %R 10.1101/258509 %J bioRxiv %P 258509 %X MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here we describe a neuroprotective function of miR-132, the miRNA most significantly down-regulated in Alzheimer’s disease. miR-132 protects mouse and human wild-type neurons and more vulnerable Tau-mutant primary neurons against amyloid β-peptide (Aβ) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death. Similarly, miR-132 attenuates PHF Tau pathology and neurodegeneration and enhances long-term potentiation in the P301S Tau transgenic mice. The neuroprotective effects are mediated by direct regulation of the Tau modifiers acetyltransferase EP300, kinase GSK3β, RNA-binding protein Rbfox1, and proteases Calpain 2 and Caspases 3/7. These data suggest miR-132 as a master regulator of neuronal health and indicate that miR-132 supplementation could be of therapeutic benefit for the treatment of Tau-associated neurodegenerative disorders. %U https://www.biorxiv.org/content/biorxiv/early/2018/02/21/258509.full.pdf