The vicious cycle: unraveling the interplay between α-synuclein, mitochondrial dysfunction, and neuroinflammation in...

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, characterized primarily by motor symptoms such as resting tremor, rigidity, and bradykinesia, accompanied by non-motor symptoms (NMS) including constipation and depression. The underlying mechanisms of PD are multifaceted, driven by a complex interaction between genetic and environmental factors that remain to be entirely understood. In recent years, an increasing body of evidence has confirmed that the abnormal aggregation of α-synuclein (α-Syn), mitochondrial dysfunction, and neuroinflammatory activation are not isolated pathological events; rather, they constitute the core driving mechanism of PD pathogenesis and progression through complex networked interactions. This narrative review examines the independent mechanisms of these three pathological components, provides an in-depth analysis of their regulatory interaction networks, and summarizes therapeutic targets and synergistic treatment strategies for the pathological axes, aiming to provide theoretical support for disease-modifying therapy and early intervention in PD.