Gut-to-Brain α-Synuclein Transmission in Parkinson's Disease: Evidence for Prion-like Mechanisms

Parkinson's disease (PD) is a multifactorial disorder involving both motor and non-motor symptoms caused by the progressive death of distinct neuronal populations, including dopaminergic neurons in the substantia nigra. The deposition of aggregated α-synuclein protein into Lewy body inclusions...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-04, Vol.24 (8), p.7205
Main Authors: Chen, Merry, Mor, Danielle E
Format: Article
Language:English
Subjects:
alpha-Synuclein - metabolism
Analysis
Animals
Brain
Brain - metabolism
Disease transmission
Dopaminergic Neurons - metabolism
Gastrointestinal system
Humans
Medical research
Medicine, Experimental
Neurons
Parkinson Disease - metabolism
Prions
Prions - metabolism
Review
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Summary:Parkinson's disease (PD) is a multifactorial disorder involving both motor and non-motor symptoms caused by the progressive death of distinct neuronal populations, including dopaminergic neurons in the substantia nigra. The deposition of aggregated α-synuclein protein into Lewy body inclusions is a hallmark of the disorder, and α-synuclein pathology has been found in the enteric nervous system (ENS) of PD patients up to two decades prior to diagnosis. In combination with the high occurrence of gastrointestinal dysfunction in early stages of PD, current evidence strongly suggests that some forms of PD may originate in the gut. In this review, we discuss human studies that support ENS Lewy pathology as a characteristic feature of PD, and present evidence from humans and animal model systems that α-synuclein aggregation may follow a prion-like spreading cascade from enteric neurons, through the vagal nerve, and into the brain. Given the accessibility of the human gut to pharmacologic and dietary interventions, therapeutic strategies aimed at reducing pathological α-synuclein in the gastrointestinal tract hold significant promise for PD treatment.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms24087205