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Link to original content: http://www.ncbi.nlm.nih.gov/pubmed/21403864
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. 2011:2011:618127.
doi: 10.1155/2011/618127. Epub 2011 Feb 24.

Hsp70 and its molecular role in nervous system diseases

Affiliations

Hsp70 and its molecular role in nervous system diseases

Giuseppina Turturici et al. Biochem Res Int. 2011.

Abstract

Heat shock proteins (HSPs) are induced in response to many injuries including stroke, neurodegenerative disease, epilepsy, and trauma. The overexpression of one HSP in particular, Hsp70, serves a protective role in several different models of nervous system injury, but has also been linked to a deleterious role in some diseases. Hsp70 functions as a chaperone and protects neurons from protein aggregation and toxicity (Parkinson disease, Alzheimer disease, polyglutamine diseases, and amyotrophic lateral sclerosis), protects cells from apoptosis (Parkinson disease), is a stress marker (temporal lobe epilepsy), protects cells from inflammation (cerebral ischemic injury), has an adjuvant role in antigen presentation and is involved in the immune response in autoimmune disease (multiple sclerosis). The worldwide incidence of neurodegenerative diseases is high. As neurodegenerative diseases disproportionately affect older individuals, disease-related morbidity has increased along with the general increase in longevity. An understanding of the underlying mechanisms that lead to neurodegeneration is key to identifying methods of prevention and treatment. Investigators have observed protective effects of HSPs induced by preconditioning, overexpression, or drugs in a variety of models of brain disease. Experimental data suggest that manipulation of the cellular stress response may offer strategies to protect the brain during progression of neurodegenerative disease.

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Figures

Figure 1
Figure 1
Domain structure of Hsp70.
Figure 2
Figure 2
Schematic of ATP hydrolysis and the role of cochaperones.
Figure 3
Figure 3
Pharmacological activation of HSF1 by small chemical activators and induction of molecular chaperones genes (hsp). 17-AAG:17-(allylamino)-17-demethoxygeldanamycin, 17-DMAG: 17-dyimethylaminoethylamino-17-demethoxygeldanamycin.

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