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Memory Decline and Its Reversal in Aging and Neurodegeneration Involve miR-183/96/182 Biogenesis.
Jawaid, Ali; Woldemichael, Bisrat T; Kremer, Eloïse A; Laferriere, Florent; Gaur, Niharika; Afroz, Tariq; Polymenidou, Magdalini; Mansuy, Isabelle M.
Afiliação
  • Jawaid A; Laboratory of Neuroepigenetics, Neuroscience Center Zürich, University of Zurich (UZH) and Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
  • Woldemichael BT; Laboratory of Neuroepigenetics, Neuroscience Center Zürich, University of Zurich (UZH) and Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
  • Kremer EA; Icahn school of medicine at Mount Sinai, New York, USA.
  • Laferriere F; Laboratory of Neuroepigenetics, Neuroscience Center Zürich, University of Zurich (UZH) and Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
  • Gaur N; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Afroz T; Laboratory of Neuroepigenetics, Neuroscience Center Zürich, University of Zurich (UZH) and Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
  • Polymenidou M; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Mansuy IM; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Mol Neurobiol ; 56(5): 3451-3462, 2019 May.
Article em En | MEDLINE | ID: mdl-30128653
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / MicroRNAs / Transtornos da Memória / Degeneração Neural Limite: Animals / Humans Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / MicroRNAs / Transtornos da Memória / Degeneração Neural Limite: Animals / Humans Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça