Toxin-induced animal models in Parkinson's disease: Recent updates

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder primarily affecting older adults. It is characterized by motor symptoms such as tremor, rigidity, and bradykinesia, resulting from the degeneration of dopaminergic neurons in the substantia nigra pars compacta. While PD's etiology is multifaceted, toxin-induced models have significantly advanced our understanding of its pathogenesis and potential treatments. Key environmental neurotoxins used in PD research include 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-hydroxydopamine, paraquat, and rotenone. These compounds can cross the blood-brain barrier and selectively damage dopamine neurons, mimicking PD pathology through mechanisms involving mitochondrial dysfunction, oxidative stress, and neuroinflammation. Researchers use various model systems to study toxin-induced PD, including rodents, primates, zebrafish, and invertebrates. The effectiveness of these models depends on the route of administration and concentration of neurotoxins. Understanding these parameters is crucial for accurately reproducing Parkinsonian features in research settings and developing novel therapeutic strategies. © 2026 Elsevier Inc. All rights reserved.