Heat Shock Proteins and Protection of the Nervous System
- 1 October 2007
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 1113 (1), 147-158
- https://doi.org/10.1196/annals.1391.032
Abstract
Manipulation of the cellular stress response offers strategies to protect brain cells from damage induced by ischemia and neurodegenerative diseases. Overexpression of Hsp70 reduced ischemic injury in the mammalian brain. Investigation of the domains within Hsp70 that confer ischemic neuroprotection revealed the importance of the carboxyl-terminal domain. Arimoclomol, a co-inducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in which motor neurons in the spinal cord and motor cortex degenerate. Celastrol, a promising candidate as an agent to counter neurodegenerative diseases, induced expression of a set of Hsps in differentiated neurons grown in tissue culture. Heat shock 'preconditioning' protected the nervous system at the functional level of the synapse and selective overexpression of Hsp70 enhanced the level of synaptic protection. Following hyperthermia, constitutively expressed Hsc70 increased in synapse-rich areas of the brain where it associates with Hsp40 to form a complex that can refold denatured proteins. Stress tolerance in neurons is not solely dependent on their own Hsps but can be supplemented by Hsps from adjacent glial cells. Hence application of exogenous Hsps at neural injury sites is an effective strategy to maintain neuronal viability.Keywords
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