Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity.
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.
Cleren
Carine
C
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York, USA.
Calingasan
Noel Y
NY
Chen
Junya
J
Beal
M Flint
MF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D005911:Gliosis / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000506:poisoning; D009574:Nitro Compounds; D053978:Pentacyclic Triterpenes; D011422:Propionates / Q000037:antagonists & inhibitors / Q000506:poisoning*; D051381:Rats; D011917:Rats, Inbred Lew; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018492:Dopamine Antagonists; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D053978:Pentacyclic Triterpenes; D011422:Propionates; D014315:Triterpenes; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C050414:celastrol; C015392:3-nitropropionic acid; D004298:Dopamine