A Brief Overview of Gut-Associated <b>α</b>-Synuclein Pathology

Lewy body diseases (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), are neurodegenerative disorders characterized by the intracellular aggregation and accumulation of α-Synuclein (αSyn), leading to neuronal death. Although these diseases primarily present with symptoms affecting the central nervous system (CNS), such as motor and cognitive impairment, increasing research suggests that their roots may be found in the gut. This review summarizes recent findings and key historical insights into the involvement of the gut in αSyn pathology. The topics covered include pathological observations in patients with LBD, animal models investigating the propagation of αSyn from the gut to the brain, intestinal inflammation, alterations in the gut microbiome, and the molecular mechanisms of αSyn pathology within enteric neurons. These topics are essential for understanding the involvement of the gut in αSyn pathology and provide foundational insights that may lead to future therapeutic applications.