α-Synuclein-Based Animal Models of Parkinson's Disease: Challenges and Opportunities in a New Era

In recent years, a new generation of animal models of Parkinson's disease (PD) based on ectopic expression, overexpression, or intracerebral injection of the protein α-synuclein have emerged. Critically, these models develop inclusions of aggregated α-synuclein and/or α-synuclein-mediated neuronal loss replicating the defining pathological hallmarks of PD and driving significant advances in the understanding of the pathogenic mechanisms underpinning PD. Here, we provide a comprehensive review of this new generation of animal models of PD, ranging from invertebrate to rodent to nonhuman primate. We focus on their strengths and limitations with respect to their highly anticipated contribution to the further understanding of α-synuclein pathobiology and the future testing of novel disease-modifying therapeutics.