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

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by motor impairment, resulting from the accumulation of alpha-synuclein and neuronal cell death in the substantia nigra of the midbrain. Emerging evidence suggests that alpha-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 alpha-synuclein aggregation within the framework of gut-originated PD pathogenesis. It begins by discussing evidence linking dysbiosis and intestinal inflammation to alpha-synuclein aggregation in the ENS. Additionally, it explores the potential role of intestinal immune cells in influencing enteric neurons and alpha-synuclein aggregation, furthering the understanding of PD development.