Cadmium (Cd), a toxic environmental pollutant, can readily accumulate in human body by Cd-contaminated environment or food chain,andevokemulti-organ toxicity. Especially, Cd can directly traverse the blood-brain barrier, which is considered as an important factor of neuronal apoptosis/neurodegenerative diseases. Celastrol, a pentacyclic triterpene with anti-inflammatory and antioxidant effects, is extracted from plants. Recently, Prof. Long Chen’s research group fromCollege of Life Science published a series of papers, revealing the important molecular mechanismsforcelastrol’sprevention fromCd neurotoxicity. They found that: i)Celastrol blocks Cd-induced activation of mTOR and neuronal apoptosis by preventing mitochrondia ROS inactivation of AMPK; ii)Celastrol attenuates cadmium-induced neuronal apoptosis via inhibiting Ca2+-CaMKII-dependent Akt/mTOR pathway; iii)Celastrol ameliorates Cd-induced neuronal apoptosis by targeting NOX2-derived ROS-dependent PP5-JNK signaling pathway. These findings highlight that celastrol might be exploited for the prevention of Cd-induced neuronal apoptosis/neurodegenerative disorders.
The above findings have been published on internationally renowned journals such as British Journal of Pharmacology (2017;174:82-100. SCI IF=5.259), Journal of Cellular Physiology (2017; doi:10.1002/jcp.25703. SCI IF= 4.155) and Journal of Neurochemistry (2017; doi:10.1002/jcp.25703. SCI IF= 3.842) with the titles 'Celastrol prevents cadmium-induced neuronal cell death by blocking reactive oxygen species-mediated mammalian target of rapamycin pathway', 'Celastrol attenuates cadmium-induced neuronal apoptosis via inhibiting Ca2+-CaMKII-dependent Akt/mTOR pathway' and 'Celastrol ameliorates Cd-induced neuronal apoptosis by targeting NOX2-derived ROS-dependent PP5-JNK signaling pathway'. The first authors of these papers are Ruijie Zhang,a PhD student, and Chong Xu Ph.D., respectively.
This series of work was supported partly by the grants from National Natural Science Foundation of China (NSFC), Project for the Priority Academic Program Development and the Natural Science Foundation of Jiangsu Higher Education Institutions of China (PAPD), National Institutes of Health (NIH), and Innovative Research Program of Jiangsu College Graduate of China.