敲除α-突触核蛋白保护多巴胺能神经元
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敲除α-突触核蛋白保护多巴胺能神经元
甲基苯丙胺诱导的帕金森病模型中多巴胺能神经元死亡的主要因素是α-突触核蛋白过表达。中国南方医科大学王慧君博士所在团队发现,立体定位注射α-syn-shRNA慢病毒抑制右侧纹状体α-syn mRNA和蛋白的表达后,帕金森病模型大鼠抑郁表现减弱,且纹状体中多巴胺水平和酪氨酸羟化酶及超氧化物歧化酶活性显著增加,而活性氧生成量、一氧化氮合酶活性、一氧化氮含量和丙二醛含量下降,同时纹状体中凋亡细胞的数量明显降低。作者认为,α-突触核蛋白具有通过抑制氧化应激和改善多巴胺能系统功能扭转甲基苯丙胺诱导的神经毒性的能力。相关文献发表于《中国神经再生研究(英文版)》杂志2014年5月第9期。
TUNEL染色结果显示,以立体定向注射α-syn-shRNA慢病毒敲除右侧纹状体中α-syn后,腹腔注射甲基苯丙胺建立帕金森病模型大鼠纹状体中凋亡细胞的数量显著降低
Article: " Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons," by Yunchun Tai1, Ling Chen1, Enping Huang1, Chao Liu1, 2, Xingyi Yang1, Pingming Qiu1, Huijun Wang1 (1 Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong
Province, China; 2 Guangzhou Forensic Science Institute, Guangzhou, Guangdong Province, China)
Tai YC, Chen L, Huang EP, Liu C, Yang XY, Qiu PM, Wang HJ. Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons. Neural Regen Res. 2014;9(9):951-958.
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Neural Regen Res
Protective effect of α-synuclein knockdown on dopaminergic neurons
The over-expression of α-synuclein is a major factor in the death of dopaminergic neurons in a methamphetamine-induced model of Parkinson’s disease (PD). Dr. Huijun Wang, School of Basic Medical Sciences, Southern Medical University, China and his team injected α-synuclein-shRNA lentivirus stereotaxically into the right striatum of experimental r ats to inhibit α-synuclein mRNA and protein expression. Results showed that after α-synuclein knockdown, the depression manifestations of PD rats were reduced, striatal dopamine and tyrosine hydroxylase levels as well as superoxide dismutase activity were significantly increased, but the levels of reactive oxygen species, malondialdehyde, nitric oxide synthase and nitrogen monoxide were decreased, and simultaneously, the number of apoptotic cells in the striatum was significantly decreased. The authors considered α-synuclein has the capacity to reverse methamphetamine-induced apoptosis of dopaminergic neurons in the rat striatum by inhibiting oxidative stress and improving dopaminergic system function. Related results were published in Neural Regeneration Research (V ol. 9, No. 9, 2014).
After α-synuclein knockdown by stereotaxic injection of α-synuclein into the right striatum, the number of apoptotic cells in the striatum of rat models of mtamfetamine-induced Alzheimer’s disease was significantly reduced, as shown by TUNEL staining.
Article: " Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons," by Yunchun Tai1, Ling Chen1, Enping Huang1, Chao Liu1, 2, Xingyi Yang1, Pingming Qiu1, Huijun Wang1 (1 Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong
Province, China; 2 Guangzhou Forensic Science Institute, Guangzhou, Guangdong Province, China)
Tai YC, Chen L, Huang EP, Liu C, Yang XY, Qiu PM, Wang HJ. Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons. Neural Regen Res. 2014;9(9):951-958.