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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511873PMC
http://dx.doi.org/10.1111/acel.13189DOI Listing

Publication Analysis

Top Keywords

memory capacity
12
autophagy agonists
8
autophagy agonist
8
age-related memory
8
memory decline
8
amyloid fibrils
8
memory
6
autophagy
5
mechanisms autophagy
4
autophagy regulates
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!