Celastrol as a neuroprotective drug: current status and challenges

Neurological disorders are increasing worldwide, imposing a major social and economic burden. Therefore, there is an urgent need to explore effective treatment methods to alleviate neurological disorders. Celastrol, derived from the traditional Chinese medicine Tripterygium wilfordii Hook. f., has been shown in multiple studies to exhibit promising neuroprotective effects in neurodegenerative, including Parkinson's disease, Alzheimer's disease, and spinal cord injury. The targets or pathways through which celastrol exerts its neuroprotective effects are diverse. This paper primarily focuses on in vivo animal models (such as Parkinson's disease mouse models, Alzheimer's disease mouse models) and in vitro cell models (such as neuronal cell lines, primary cultured neurons) experiments to comprehensively summarize the molecular mechanisms underlying celastrol's neuroprotective effects. Celastrol exerts its neuroprotective effects through pathways such as reducing inflammation, activating the autophagy-lysosome pathway, and inhibiting ferroptosis. Additionally, we discuss the current challenges faced by celastrol and potential strategies to address them. Collectively, these findings highlight celastrol as a promising therapeutic candidate, although further pharmacokinetic optimization and clinical validation are essential.