Zebrafish Models of Parkinson's Disease: From Pathogenesis to Drug Discovery

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of Lewy bodies, composed of the protein α-synuclein, and the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta. The management of PD seeks to mitigate motor symptoms by substituting diminished endogenous dopamine; nevertheless, it does not halt disease progression. Various animal models have been employed to elucidate the etiology of PD and to discover disease-modifying treatments. Zebrafish serve as a PD model owing to their capacity for high-throughput screening. This review presents updates on the currently available zebrafish models of PD, encompassing both chemically induced and genetically based models, and discusses their advantages and limitations. This review also delineates numerous investigative strategies that utilize the zebrafish PD model and summarizes the findings of previous studies. Taken together, further studies, including the investigation of the regeneration mechanism of DA neurons, neurobehavioral testing of adult zebrafish reflecting PD-associated neurocognitive impairment, and a reliable gene-based model providing precise gene knockout and reproducibility, may assist in elucidating the critical pathways that trigger PD and its progression, alongside potential targets to hinder this progression.