Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity

被引：168

作者：

Cleren, C ^{[1
]}

Calingasan, NY ^{[1
]}

Chen, J ^{[1
]}

Beal, MF ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York Presbyterian Hosp, New York, NY USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2005年 / 94卷 / 04期

关键词：

celastrol; gliosis; heat shock protein 70; Huntington; inflammation; Parkinson;

D O I：

10.1111/j.1471-4159.2005.03253.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：995 / 1004

页数：10

共 45 条

[1] Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease [J].