Towards zebrafish model applications in drug discovery targeting central nervous system diseases and neurotoxicity...

Zebrafish have emerged as a pivotal model for drug discovery targeting central nervous system (CNS) diseases and neurotoxicity assessment, leveraging their genetic, anatomical, and functional similarities to humans. Despite their growing utilization, comprehensive reviews integrating both applications are scarce. Critical challenges persist in standardizing models and improving the accuracy and reliability of experimental outcomes. This review compares the human and zebrafish CNS, highlighting sex-specific difference, examines behavioural assays for disease modeling and neurotoxicity studies. It focuses on zebrafish application in drug discovery for stroke and Alzheimer's disease (AD), and neurotoxicity assessment, highlighting their preclinical value. To address ongoing challenges, further efforts should prioritize standardized guidelines, improved reproducibility and advanced genetic engineering to optimize zebrafish models. These advancements will solidify zebrafish as an indispensable tool for accelerating CNS drug development and neurotoxicity evaluation, addressing critical global health challenges.