Animal Models of Parkinson’s Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta, the consequent dopamine deficit in the striatum and the accumulation of aggregated α‐synuclein (α‐syn) in specific brain regions. The underlying pathophysiology of PD remains poorly understood. Animal models are the best tools to study the pathogenesis of PD. Most studies in PD animal models have focused on the motor features associated with dopamine depletion but still the molecular basis of PD and the molecular pathways of cell death remain unknown. While cellular models have helped to identify specific events, in vivo animal models have simulated most, although not all, of the hallmarks of PD and are useful for testing new neuroprotective approaches. In this chapter, we provide a summary of the most used PD animal models, including their advantages and limitations. Classically, in vivo PD animal models can be divided into those using environmental or synthetic neurotoxins (toxin‐based models) or those utilizing the in vivo expression of PD‐related mutations (genetic models). These models include 6‐hydroxydopamine (6‐OHDA), 1‐methyl‐1,2,3,6‐tetrahydropyridine (MPTP), rotenone, and paraquat, as well as genetic models such as those related to α‐syn, PINK1, Parkin, DJ‐1, and LRRK2.