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International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 406561, 6 pages
http://dx.doi.org/10.1155/2012/406561
Review Article

MicroRNAs and the Regulation of Tau Metabolism

1Axe Neurosciences, Centre de Recherche du CHUQ (CHUL), Québec, QC, Canada G1V 4G2
2Département de Psychiatrie et de Neurosciences, Faculté de Médecine, Université Laval, Québec, QC, Canada G1V 0A6
3Faculté de Médecine, Université Lille-Nord de France, UDSL, 59044 Lille, France
4Inserm, UMR837, 59045 Lille, France

Received 24 February 2012; Accepted 19 April 2012

Academic Editor: Lars M. Ittner

Copyright © 2012 Sébastien S. Hébert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Abnormal regulation of tau phosphorylation and/or alternative splicing is associated with the development of a large (>20) group of neurodegenerative disorders collectively known as tauopathies, the most common being Alzheimer's disease. Despite intensive research, little is known about the molecular mechanisms that participate in the transcriptional and posttranscriptional regulation of endogenous tau, especially in neurons. Recently, we showed that mice lacking Dicer in the forebrain displayed progressive neurodegeneration accompanied by disease-like changes in tau phosphorylation and splicing. Dicer is a key enzyme in the biogenesis of microRNAs (miRNAs), small noncoding RNAs that function as part of the RNA-induced silencing complex (RISC) to repress gene expression at the posttranscriptional level. We identified miR-16 and miR-132 as putative endogenous modulators of neuronal tau phosphorylation and tau exon 10 splicing, respectively. Interestingly, these miRNAs have been implicated in cell survival and function, whereas changes in miR-16/132 levels correlate with tau pathology in human neurodegenerative disorders. Thus, understanding how miRNA networks influence tau metabolism and possibly other biological systems might provide important clues into the molecular causes of tauopathies, particularly the more common but less understood sporadic forms.