Premium
Celastrol protects against MPTP‐ and 3‐nitropropionic acid‐induced neurotoxicity
Author(s) -
Cleren Carine,
Calingasan Noel Y.,
Chen Junya,
Beal M. Flint
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03253.x
Subject(s) - celastrol , mptp , substantia nigra , pars compacta , neuroprotection , dopaminergic , neurotoxin , pharmacology , dopamine , chemistry , neurodegeneration , neurotoxicity , oxidative stress , endocrinology , medicine , biochemistry , toxicity , apoptosis , disease
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‐α and nuclear factor κ B immunostainings as well as astrogliosis. Celastrol is therefore a promising neuroprotective agent for the treatment of PD and HD.