The core pathological feature of Parkinson’s disease (PD) is the abnormal aggregation of αsynuclein and the result ing neuronal damage. α-Synuclein exhibits toxic effects when it forms oligomers or fibrils, leading to neuronal death via multiple pathways, including mitochondrial dysfunction, impaired vesicular trafficking, dopamine auto-oxidation, and neuroinflammation. In addition, α-synuclein can propagate between cells via exosomes, endocytosis/exocytosis, tunneling nanotubes, or vagal nerve axonal transport, creating a cascade of pathological effects. Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions. To date, various strategies, including transgenic techniques, bacterial artificial chromosome (BAC)-mediated expression, viral vector-mediated overexpression, and gene editing, have been employed to develop α-synuclein overexpression animal models. These models have significantly advanced our exploration of the relationship between PD and α-synuclein. This systematic review considers the structure and function of α-synuclein, its mechanisms of toxicity, intercellular propagation pathways, animal models of overexpression, and potential therapeutic targets based on its pathogenic mechanisms.