Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity
Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity
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DOI：
10.1111/j.1471-4159.2005.03253.x
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发表时间：
2005-08-01
影响因子：
4.7
通讯作者：
Beal, MF
中科院分区：
文献类型：
--
作者：
Cleren, C;Calingasan, NY;Beal, MF
氧化应激和炎症与神经退行性疾病包括帕金森病（PD）和亨廷顿病（HD）有关。南蛇藤酚是从属于卫矛科的多年生匍匐植物中提取的有效抗炎和抗氧化化合物。已知雷公藤红素可防止促炎细胞因子、诱导型一氧化氮合酶和脂质过氧化的产生。在注射MPTP（一种多巴胺能神经毒素，其产生PD模型）之前和之后，用雷公藤红素处理小鼠。雷公藤红素治疗可显著减弱MPTP诱导的黑质丘脑腹侧部多巴胺能神经元48%的损失。此外，雷公藤红素处理显著减少了MPTP诱导的多巴胺浓度的消耗。类似地，雷公藤红素显著降低了由3-硝基丙酸（一种用于在大鼠中建立HD模型的神经毒素）诱导的纹状体病变体积。雷公藤红素诱导多巴胺能神经元内的热休克蛋白70，并降低肿瘤坏死因子-α和核因子κ B免疫染色以及星形胶质细胞增生。因此，雷公藤红素是一种有前途的神经保护剂，用于治疗PD和HD。
Oxidative stress and inflammation are implicated in neurodegenerative diseases including Parkinson's disease (PD) and Huntington's disease (HD). Celastrol is a potent anti-inflammatory and antioxidant compound extracted from a perennial creeping plant belonging to the Celastraceae family. Celastrol is known to prevent the production of proinflammatory cytokines, inducible nitric oxide synthase and lipid peroxidation. Mice were treated with celastrol before and after injections of MPTP, a dopaminergic neurotoxin, which produces a model of PD. A 48% loss of dopaminergic neurons induced by MPTP in the substantia nigra pars compacta was significantly attenuated by celastrol treatment. Moreover, celastrol treatment significantly reduced the depletion in dopamine concentration induced by MPTP. Similarly, celastrol significantly decreased the striatal lesion volume induced by 3-nitropropionic acid, a neurotoxin used to model HD in rats. Celastrol induced heat shock protein 70 within dopaminergic neurons and decreased tumor necrosis factor-alpha and nuclear factor kappa B immunostainings as well as astrogliosis. Celastrol is therefore a promising neuroprotective agent for the treatment of PD and HD.