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.
Mechanisms by which autophagy regulates memory capacity in ageing / M. De Risi, G. Torromino, M. Tufano, S. Moriceau, A. Pignataro, M. Rivagorda, N. Carrano, S. Middei, C. Settembre, M. Ammassari-Teule, F. Gardoni, A. Mele, F. Oury, E. De Leonibus. - In: AGING CELL. - ISSN 1474-9718. - 19:9(2020 Jul 30).
|Titolo:||Mechanisms by which autophagy regulates memory capacity in ageing|
|Parole Chiave:||ageing; alpha-synuclein; amyloid fibrils; autophagy; GluA1; mild cognitive impairment; Spermidine|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||30-lug-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/acel.13189|
|Appare nelle tipologie:||01 - Articolo su periodico|