Mechanisms by which autophagy regulates memory capacity in ageing

Maria De Risi, Giulia Torromino, Michele Tufano, Stéphanie Moriceau, Annabella Pignataro, Manon Rivagorda, Nicolò Carrano, Silvia Middei, Carmine Settembre, Martine Ammassari-Teule, Fabrizio Gardoni, Andrea Mele, Franck Oury, Elvira De Leonibus

Abstract

Autophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age-related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle-aged (12-month-old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (β-amyloid and α-synuclein) and impaired task-induced GluA1 hippocampal post-translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT-Beclin 1 rescued memory capacity and GluA1 post-translational modifications by favouring the autophagy/lysosomal-mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age-related memory decline.

OriginalspracheEnglisch
ZeitschriftAging Cell
Jahrgang19
Ausgabenummer9
Seiten (von - bis)e13189
ISSN1474-9718
DOIs
PublikationsstatusVeröffentlicht - 09.2020

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

DFG-Fachsystematik

  • 205-09 Pharmakologie

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