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Review
. 2025 Jul;46(7):2965-2977.
doi: 10.1007/s10072-025-08114-w. Epub 2025 Mar 14.

The interrelationship between intestinal immune cells and enteric α-synuclein in the progression of Parkinson's disease

Yuan-Kai Cheng  1 , Hao-Sen Chiang  2   3
Affiliations
Review

The interrelationship between intestinal immune cells and enteric α-synuclein in the progression of Parkinson's disease

Yuan-Kai Cheng et al. Neurol Sci. 2025 Jul.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by motor impairment, resulting from the accumulation of α-synuclein and neuronal cell death in the substantia nigra of the midbrain. Emerging evidence suggests that α-synuclein aggregation may originate in the enteric nervous system (ENS) and subsequently propagate to the brain via the vagus nerve. Clinical observations, such as prodromal gastrointestinal dysfunction in PD patients and the increased incidence of PD among individuals with inflammatory bowel disease, support the hypothesis that abnormal intestinal inflammation may contribute to the onset of motor dysfunction and neuropathology in PD. This review examines recent findings on the interplay between intestinal immune cells and α-synuclein aggregation within the framework of gut-originated PD pathogenesis. It begins by discussing evidence linking dysbiosis and intestinal inflammation to α-synuclein aggregation in the ENS. Additionally, it explores the potential role of intestinal immune cells in influencing enteric neurons and α-synuclein aggregation, furthering the understanding of PD development.

Keywords: Alpha-synuclein; Dysbiosis; Enteric nervous system; Inflammatory bowel diseases; Intestinal immune cells; Intestinal inflammation; Parkinson’s disease.

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Conflict of interest statement

Declarations. Competing interest: The authors declare no competing interests. Generative AI and AI-assisted technologies in the writing process: During the preparation of this work the authors used ChatGPT in order to improve the readability and language of the manuscript. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. Ethics statement: This study is a systematic review of published studies; therefore, ethics approval was not required. Ethical approval and Informed consent statement: None. This work was supported by the National Science and Technology Council, Taiwan [grant numbers: 113-2314-B-002-300 and 113-2320-B-002-028 to H.-S.C].

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