Super-resolution imaging reveals α-synuclein seeded aggregation in SH-SY5Y cells.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
21 05 2021
21 05 2021
Historique:
received:
19
12
2020
accepted:
20
04
2021
entrez:
22
5
2021
pubmed:
23
5
2021
medline:
10
8
2021
Statut:
epublish
Résumé
Aggregation of α-synuclein (α-syn) is closely linked to Parkinson's disease (PD) and the related synucleinopathies. Aggregates spread through the brain during the progression of PD, but the mechanism by which this occurs is still not known. One possibility is a self-propagating, templated-seeding mechanism, but this cannot be established without quantitative information about the efficiencies and rates of the key steps in the cellular process. To address this issue, we imaged the uptake and seeding of unlabeled exogenous α-syn fibrils by SH-SY5Y cells and the resulting secreted aggregates, using super-resolution microscopy. Externally-applied fibrils very inefficiently induced self-assembly of endogenous α-syn in a process accelerated by the proteasome. Seeding resulted in the increased secretion of nanoscopic aggregates (mean 35 nm diameter), of both α-syn and Aβ. Our results suggest that cells respond to seed-induced disruption of protein homeostasis predominantly by secreting nanoscopic aggregates; this mechanism may therefore be an important protective response by cells to protein aggregation.
Identifiants
pubmed: 34021258
doi: 10.1038/s42003-021-02126-w
pii: 10.1038/s42003-021-02126-w
pmc: PMC8139990
doi:
Substances chimiques
Amyloid
0
Protein Aggregates
0
SNCA protein, human
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
613Subventions
Organisme : Parkinson's UK
ID : G-1703
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
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