Roles of αsynuclein in gastrointestinal microbiome dysbiosisrelated Parkinson's disease progression (Review).
Mol Med Rep
; 24(4)2021 10.
Article
in English
| MEDLINE | ID: covidwho-1395037
ABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middleaged and elderly populations. Several studies have confirmed that the microbiotagutbrain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of αsynuclein (αsyn) in the intestine. Abnormal αsyn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of αsyn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of αsyn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of αsyn in the intestine caused by the GM changes and the increased levels of αsyn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing αsyn accumulation to relieve the symptoms and progression of PD are described.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Parkinson Disease
/
Disease Progression
/
Alpha-Synuclein
/
Gastrointestinal Microbiome
/
Brain-Gut Axis
Type of study:
Prognostic study
Limits:
Aged
/
Humans
/
Middle aged
Language:
English
Year:
2021
Document Type:
Article
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