Acidic nanoparticles protect against α-synuclein-induced neurodegeneration through the restoration of lysosomal function.
Parkinson's disease
acidic nanoparticles
alpha-synuclein, neurodegeneration, therapeutics
in vivo
lysosomal restoration
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
11
01
2022
received:
25
08
2021
accepted:
01
02
2022
pubmed:
24
3
2022
medline:
16
4
2022
entrez:
23
3
2022
Statut:
ppublish
Résumé
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, associated with the accumulation of misfolded α-synuclein and lysosomal impairment, two events deemed interconnected. Protein aggregation is linked to defects in degradation systems such as the autophagy-lysosomal pathway, while lysosomal dysfunction is partly related to compromised acidification. We have recently proven that acidic nanoparticles (aNPs) can re-acidify lysosomes and ameliorate neurotoxin-mediated dopaminergic neurodegeneration in mice. However, no lysosome-targeted approach has yet been tested in synucleinopathy models in vivo. Here, we show that aNPs increase α-synuclein degradation through enhancing lysosomal activity in vitro. We further demonstrate in vivo that aNPs protect nigral dopaminergic neurons from cell death, ameliorate α-synuclein pathology, and restore lysosomal function in mice injected with PD patient-derived Lewy body extracts carrying toxic α-synuclein aggregates. Our results support lysosomal re-acidification as a disease-modifying strategy for the treatment of PD and other age-related proteinopathies.
Identifiants
pubmed: 35318803
doi: 10.1111/acel.13584
pmc: PMC9009122
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13584Informations de copyright
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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