Mechanisms by which autophagy regulates memory capacity in ageing
| Autor: | Andrea Mele, Maria De Risi, Martine Ammassari-Teule, Manon Rivagorda, Annabella Pignataro, Nicolò Carrano, Silvia Middei, Giulia Torromino, Carmine Settembre, Elvira De Leonibus, Fabrizio Gardoni, Michele Tufano, Stéphanie Moriceau, Franck Oury |
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| Přispěvatelé: | De Risi, M., Torromino, G., Tufano, M., Moriceau, S., Pignataro, A., Rivagorda, M., Carrano, N., Middei, S., Settembre, C., Ammassari-Teule, M., Gardoni, F., Mele, A., Oury, F., De Leonibus, E. |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Agonist autophagy Aging Spermidine medicine.drug_class alpha-synuclein Biology amyloid fibrils Mice 03 medical and health sciences chemistry.chemical_compound mild cognitive impairment 0302 clinical medicine Memory amyloid fibril medicine Animals Cognitive Dysfunction Alpha-synuclein Neurodegeneration Autophagy Original Articles Cell Biology Impaired memory medicine.disease Cell biology Disease Models Animal alpha‐synuclein 030104 developmental biology chemistry ageing Ageing Synaptic plasticity Original Article GluA1 030217 neurology & neurosurgery |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| Popis: | 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. We developed a novel mouse model of mild cognitive impairment (MCI) that allows to identify middle‐aged (12‐month‐old) mice with impaired memory capacity and vulnerable to age‐dependent memory decline. Spermidine and TAT‐Beclin 1, by stimulating autophagy/lysosomal degradation of misfolded protein, reduce the amyloid load and rescue the memory‐dependent post‐translational modifications of GluA1 receptors in the hippocampus of the cognitively impaired ageing mice. |
| Databáze: | OpenAIRE |
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