Chinese herbal medicines for the treatment of spinocerebellar ataxia type 17 via inhibition of excitotoxicity

• Main Author: 徐銘亨
• Other Authors: Chung-Hsin Wu
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/87137626074978221404

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 101 === Excitotoxicity induced neurodegeneration, and polyglutamine (polyQ) diseases, such as Alzheimer’s disease, and Parkinson’s disease, via glutamatergic activation, resulting in excessive calcium influx, cytochrome C release from mytochondria, pro-apoptotic protein activation, and finally leads to decrease the cell viability. It was believed that Chinese herbal medicines (CHMs) might be one of new approaches to treat neurodegenerative diseases. Therefore, we investigated whether CHMs could protect neurons from monosodium glutamate (MSG)-induced excitotoxicity in human neuroblastoma SH-SY5Y cells and doxycycline (DOX) induced-nTBP-EGFP expression in spinocerebellar ataxia type 17 (SCA17) nTBP/Q79-EGFP cells. Our study showed that NH018 and its active compound NH018-1 were effective against MSG induced neurotoxicity by increasing the cell viability measured by MTT assay, and decreased the LDH release and the production of reactive oxygen species, and deduced cell apoptosis after MSG treatment in SH-SY5Y cells, DOX induced SCA17 nTBP/Q79-EGFP cells. NH018-1 also showed the remarkably protective activity against the neuronal cell death as demonstrated by : (1) reducing the Annexin V-FITC and Propidium Iodide (PI) staining, (2) the decrease of cytochrome C released from mitochondria, (3) the reduction of apoptosis-related proteins such as m-calpain (calpain-2), cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP expression, (4) the decrease of survival-related proteins such as Bcl-2, and (5) the improving of SCA17 mice performance in rotarod and footprint experiments. In conclusion, present studies showed that NH018 and NH018-1 protect cell viability after MSG treatment in SH-SY5Y cells, and DOX treatment in SCA17 nTBP/Q79-EGFP cells by inhibition of cell apoptosis. Furthermore, NH018-1 of NH018 could improve the SCA17 mice performance in rotarod test and footprint analysis as well as decrease the expression of TATA box-binding protein (TBP), calpain-2, and cleaved-caspase-3. Thus, NH018 and NH018-1 could be potential CHMs for the treatment neurodegenerative diseases.