Fine Particulate Matter Triggers α-Synuclein Fibrillization and Parkinson-like Neurodegeneration.
Mov Disord
; 37(9): 1817-1830, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-36054165
ABSTRACT
BACKGROUND:
The deposition of α-synuclein (α-Syn) in the brain is the pathological hallmark of Parkinson's disease (PD). Epidemiological data indicate that exposure to fine particulate matter (≤2.5 µm in aerodynamic diameter [PM2.5]) is associated with an increased risk for PD.OBJECTIVE:
The aim of this study is to investigate whether PM2.5 has a direct effect on α-Syn pathology and how it drives the risk for PD.METHODS:
PM2.5 was added into α-Syn monomers and different cell models to test whether PM2.5 can promote the fibrillization and aggregation of α-Syn. α-Syn A53T transgenic mice and α-Syn knockout mice were used to investigate the effects of PM2.5 on PD-like pathology.RESULTS:
PM2.5 triggers the fibrillization of α-Syn and promotes the formation of α-Syn fibrils with enhanced seeding activity and neurotoxicity. PM2.5 also induces mitochondrial dysfunction and oxidative stress. Intrastriatal injection or intranasal administration of PM2.5 exacerbates α-Syn pathology and dopaminergic neuronal degeneration in α-Syn A53T transgenic mice. The detrimental effect of PM2.5 was attenuated in α-Syn knockout mice.CONCLUSIONS:
Our results identify that PM2.5 exposure could promote the α-Syn pathology, providing mechanistic insights into how PM2.5 increases the risk for PD. © 2022 International Parkinson and Movement Disorder Society.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Sinucleinopatias
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article