RT Journal Article
SR Electronic
T1 MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 258509
DO 10.1101/258509
A1 Rachid El Fatimy
A1 Shaomin Li
A1 Zhicheng Chen
A1 Tasnim Mushannen
A1 Sree Gongala
A1 Zhiyun Wei
A1 Darrick T. Balu
A1 Rosalia Rabinovsky
A1 Adam Cantlon
A1 Abdallah Elkhal
A1 Dennis J. Selkoe
A1 Kai C. Sonntag
A1 Dominic M. Walsh
A1 Anna M. Krichevsky
YR 2018
UL http://biorxiv.org/content/early/2018/02/21/258509.abstract
AB 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.