Huang Ding-Siang, Lin Hsuan-Yuan, Lee-Chen Guey-Jen, Hsieh-Li Hsiu-Mei, Wu Chung-Hsin, Lin Jung-Yaw
Department of Life Science, National Taiwan Normal University, Taipei City, Taiwan, Republic of China.
Department of Life Science, National Taiwan Normal University, Taipei City, Taiwan, Republic of China; Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei City, Taiwan, Republic of China.
Drug Des Devel Ther. 2016 Feb 18;10:723-31. doi: 10.2147/DDDT.S98156. eCollection 2016.
Spinocerebellar ataxia type 17 (SCA 17) is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP) gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day) could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.
17型脊髓小脑共济失调（SCA 17）是一种由TATA盒结合蛋白（TBP）基因中CAG/CAA重复序列扩增引起的多聚谷氨酰胺疾病。银杏叶提取物EGb 761含有黄酮类化合物和萜类化合物，具有治疗阿尔茨海默病和帕金森病等神经退行性疾病的潜在用途。EGb 761的神经保护作用明显，但EGb 761对SCA 17是否具有治疗作用仍不清楚。为了解决我们的问题，我们构建了表达TBP/79Q的SH-SY5Y细胞和携带突变hTBP基因的SCA 17转基因小鼠。在体外实验中，我们观察到EGb 761处理降低了表达TBP/79Q的SH-SY5Y细胞中十二烷基硫酸钠不溶性蛋白的含量。我们进一步发现，EGb 761处理可以抑制兴奋性毒性和钙内流，并降低谷氨酸处理的SH-SY5Y神经母细胞瘤细胞中凋亡标志物的表达。在体内实验中，我们观察到EGb 761处理（每天腹腔注射100 mg/kg）可以缓解SCA 17转基因小鼠的运动缺陷。我们的研究结果提供了证据，表明EGb 761处理可以通过抑制SCA 17细胞和动物模型中的兴奋性毒性和凋亡来治疗SCA 17。因此，我们认为EGb 761可能是治疗SCA 17的潜在治疗剂。
