Memory Decline and Its Reversal in Aging and Neurodegeneration Involve miR-183/96/182 Biogenesis
Mol Neurobiol. 2018-08-20; :
DOI: 10.1007/s12035-018-1314-3
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Memory Decline and Its Reversal in Aging and Neurodegeneration Involve
miR-183/96/182 Biogenesis.
Jawaid A(1), Woldemichael BT(1)(2), Kremer EA(1), Laferriere F(3), Gaur N(1),
Afroz T(3), Polymenidou M(3), Mansuy IM(4).
Author information:
(1)Laboratory of Neuroepigenetics, Neuroscience Center Zürich, University of
Zurich (UZH) and Swiss Federal Institute of Technology (ETH), Zurich,
Switzerland.
(2)Icahn school of medicine at Mount Sinai, New York, USA.
(3)Institute of Molecular Life Sciences, University of Zurich, Zurich,
Switzerland.
(4)Laboratory of Neuroepigenetics, Neuroscience Center Zürich, University of
Zurich (UZH) and Swiss Federal Institute of Technology (ETH), Zurich,
Switzerland. .
Aging is characterized by progressive memory decline that can lead to dementia
when associated with neurodegeneration. Here, we show in mice that aging-related
memory decline involves defective biogenesis of microRNAs (miRNAs), in particular
miR-183/96/182 cluster, resulting from increased protein phosphatase 1 (PP1) and
altered receptor SMAD (R-SMAD) signaling. Correction of the defect by
miR-183/96/182 overexpression in hippocampus or by environmental enrichment that
normalizes PP1 activity restores memory in aged animals. Regulation of
miR-183/96/182 biogenesis is shown to involve the neurodegeneration-related
RNA-binding proteins TDP-43 and FUS. Similar alterations in miR-183/96/182, PP1,
and R-SMADs are observed in the brains of patients with amyotrophic lateral
sclerosis (ALS) or frontotemporal lobar degeneration (FTLD), two
neurodegenerative diseases with pathological aggregation of TDP-43. Overall,
these results identify new mechanistic links between miR-183/96/182, PP1, TDP-43,
and FUS in age-related memory deficits and their reversal.
DOI: 10.1007/s12035-018-1314-3
PMID: 30128653