Zebrafish Brain Regeneration as a Model for Neurorepair in Parkison’s Disease

Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world. Despite extensive research, its aetiology and pathogenesis remain poorly understood, often leading to delayed or missed diagnoses, especially in early-onset cases. One of the important hallmarks of PD is the progressive loss of dopaminergic neurons in the substantia nigra, which underlies the manifestation of motor symptoms. Current therapeutic interventions, which primarily offer symptomatic relief, do not alter the deteriorating course of the disease. These limitations have led to a greater emphasis on regenerating dopaminergic neurons as a potential approach for PD management. Mammals, however, exhibit limited reparative capacity in renewing cellular components of the central nervous system (CNS), making mammalian-based models unsuited for the understanding of neuroregeneration. As such, the zebrafish (Danio rerio) has emerged as a powerful model for neuroregeneration studies given its robust neurogenic potential, high proliferative capacity, and significant genetic and structural homology to the human brain. This review aimed at highlighting current findings on zebrafish neuroregeneration, with particular emphasis on 1) cellular responses and neuroinflammation following the loss of neurons and 2) brain repair through the regeneration of new neurons through sequential stages of progenitor cell proliferation, migration, and differentiation at the injured brain regions. The latest findings on the conserved neuroregenerative mechanisms in zebrafish further imply translational potential into novel therapeutic strategies against PD, such as drug discovery and activation of endogenous repair pathways. By contrasting the mammalian limitations, this review underscores advances in zebrafish neuroregeneration which could provide new therapeutic avenues for PD.