Induction of heat shock proteins in differentiated human and rodent neurons by celastrol

• Published in: Cell stress & chaperones 2007, Vol.12 (3), p.237-244
• Main Authors: Chow, Ari M., Brown, Ian R.
• Format: Article
• Language: English
• Subjects: Alzheimers disease; Animals; Cell Differentiation; Cell Line; Cell lines; Cell Survival - drug effects; Cellular differentiation; Disease models; Dose-Response Relationship, Drug; Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - metabolism; Humans; Nervous system diseases; Neurodegenerative diseases; Neurons; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - pharmacology; Original; Original Articles; Original s; Parkinson disease; Rodentia; Rodents; Species Specificity; Triterpenes - pharmacology; Up-Regulation; Viability
• ISSN: 1355-8145; 1466-1268
• DOI: 10.1379/CSC-269.1

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.