Experimental Models of Parkinson’s Disease: Strengths, Limitations, and Translational Perspectives

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of α-synuclein aggregates. Despite extensive research, the precise molecular triggers of PD remain unclear, and current treatments primarily address symptoms rather than halting disease progression. Experimental animal models have been indispensable for dissecting the pathophysiological mechanisms underlying PD and for testing novel therapeutic interventions. This review summarizes the principal animal models of PD, including rodents, non-human primates, and non-mammalian organisms such as C. elegans, Drosophila melanogaster, and zebrafish. Both genetic models—based on mutations in SNCA, LRRK2, PINK1, PARKIN, and DJ-1—and neurotoxin-induced models, such as MPTP, 6-OHDA, rotenone, paraquat, and drug-induced parkinsonism, are discussed in relation to their mechanistic fidelity and translational value. Understanding the strengths and limitations of these models is critical for bridging the gap between preclinical findings and clinical applications. Integrating insights across model systems may advance the development of disease-modifying therapies for PD-