TY - JOUR
T1 - Gut-to-Brain α-Synuclein Transmission in Parkinson’s Disease
T2 - Evidence for Prion-like Mechanisms
AU - Chen, Merry
AU - Mor, Danielle E.
N1 - Funding Information:
This work was supported by the start-up fund from the Medical College of Georgia at Augusta University, and the Department of Defense Early Investigator Research Award (PD210045 W81XWH-22-1-0545) to D.E.M.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - Parkinson’s disease
KW - alpha-synuclein
KW - enteric nervous system
KW - prion-like
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U2 - 10.3390/ijms24087205
DO - 10.3390/ijms24087205
M3 - Review article
AN - SCOPUS:85157996928
SN - 1661-6596
VL - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 8
M1 - 7205
ER -