Induction of heat shock proteins in differentiated human and rodent neurons by celastrol.
Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been termed protein misfolding disorders that are characterized by the neuronal accumulation of protein aggregates. Manipulation of the cellular stress-response involving induction of heat shock proteins (Hsps) in differentiated neurons offers a therapeutic strategy to counter conformational changes in neuronal proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Hsps are protein repair agents that provide a line of defense against misfolded, aggregation-prone proteins. These proteins are not induced in differentiated neurons by conventional heat shock. We have found that celastrol, a quinine methide triterpene, induced expression of a wider set of Hsps, including Hsp70B', in differentiated human neurons grown in tissue culture compared to cultured rodent neuronal cells. Hence the beneficial effect of celastrol against human neurodegenerative diseases may exceed its potential in rodent models of these diseases.
Chow
Ari M
AM
Centre for the Neurobiology of Stress, University of Toronto at Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
Brown
Ian R
IR
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes; D012377:Rodentia; D013045:Species Specificity; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; C491129:HSPA7 protein, human; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol