ABSTRACT Parkinson's disease (PD) is a progressive neurodegenerative disorder with a growing global burden. Current pharmacological therapies remain limited to symptomatic management, owning to an incomplete understanding of the mechanisms driving α‑synuclein aggregation and disease progression. This review provides an integrated overview of PD across epidemiological, etiological, pathophysiological, and clinical dimensions. It emphasizes established and emerging risk factors, including environmental toxins, lifestyle variables, and gut microbiota dysbiosis and delineates how peripheral–central pathways such as the gut–brain, erythrocyte–brain, and kidney–brain axes contribute to PD pathogenesis. At the molecular level, we explore key disruptions including proteostatic failure, aberrant phase separation, oxidative stress, neuroinflammation, synaptic dysfunction, iron dyshomeostasis, and impaired cholesterol metabolism. These encompass microbiome‑targeted interventions and blood‐based approaches. We further evaluate a spectrum of management strategies ranging from primary prevention and biomarker‑guided early detection to innovative experimental treatments such as cellular therapies, transfusion‑based modalities, and microbial modulation. By integrating recent advances in systemic pathophysiology with translational perspectives, this review highlights how molecular and cellular dysregulations underlie clinical phenotypes. Finally, we discuss promising biomarkers derived from microbial, inflammatory, and erythrocyte pathways that may facilitate early diagnosis and the development of disease‑modifying therapies.
Guo et al. (Mon,) studied this question.