Systematic Review of Caenorhabditis elegans Models for Mechanism Research and Drug Discovery in Parkinson’s Disease
Systematic Review of Caenorhabditis elegans Models for Mechanism Research and Drug Discovery in Parkinson’s Disease
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Original abstract
Abstract Parkinson’s disease (PD) constitutes the world’s second most widespread neurodegenerative ailment impacting the central nervous system. Its complex pathogenesis and significant heterogeneity restrict development of effective treatments, making reliable animal models indispensable for mechanistic studies and drug development. Caenorhabditis elegans ( C. elegans ) serves as a superior preclinical organism, attributed to its streamlined nervous architecture, human orthologous genes, abbreviated lifespan, and tractable genetic manipulation. Following PRISMA 2020 guidelines, this systematic review screened 1259 papers published between 2010 and 2026, retaining 50 qualified studies. This review outlines two primary approaches to establish C. elegans -based PD models: transgenic genetic strains and toxin-triggered models. We further elaborate three principal avenues for pharmaceutical investigation utilizing these platforms: restraining α‑synuclein aggregation alongside dopaminergic neuroprotection, balancing oxidative stress and sustaining mitochondrial integrity, and tuning metabolic and senescence-associated signaling cascades. This work offers a framework to dissect PD pathogenic mechanisms and expedite development of disease-modifying agents against PD.