Immunopathogenesis of Parkinson’s Disease: From Peripheral Inflammation to Neurodegeneration

Abstract

Parkinson’s disease (PD) is increasingly recognized as a multifactorial disorder in which immune dysfunction and chronic inflammation play critical pathogenic roles. This review synthesizes evidence from clinical, genetic, and experimental studies on the contribution of innate and adaptive immune responses to PD. It discusses the roles of microglia, T cells, and peripheral immune cells; the influence of autoimmune processes and gut inflammation; and the therapeutic potential of targeting immune pathways. Both central and peripheral immune alterations are implicated in PD onset and progression. Dysregulated microglial activation, abnormal T-cell responses to α-synuclein, and systemic inflammation may drive dopaminergic neurodegeneration. Moreover, autoimmune diseases, gut dysbiosis, and infections have been associated with increased PD risk. Understanding immune-mediated mechanisms offers new avenues for early diagnosis and disease-modifying treatments. Emerging immunotherapies—such as α-synuclein antibodies, inflammasome inhibitors, and TNF-targeting agents—hold promise for modifying disease trajectory and improving patient outcomes