title: Heat shock response and insulin-associated neurodegeneration.
abstract: Dysfunctional insulin and insulin-like growth factor-I (IGF-I) signaling contributes to the pathological progression of diabetes, diabetic peripheral neuropathy (DPN), Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD). Despite their prevalence, there are limited therapeutic options available for the treatment of these neurodegenerative disorders. Therefore, establishing a link between insulin/IGF-I and the pathoetiology of these diseases may provide alternative approaches toward their management. Many of the heat shock proteins (Hsps) are well-known molecular chaperones that solubilize and clear damaged proteins and protein aggregates. Recent studies suggest that modulating Hsps may represent a promising therapeutic avenue for improving insulin and IGF-I signaling. Pharmacological induction of the heat shock response (HSR) may intersect with insulin/IGF-I signaling to improve aspects of neurodegenerative phenotypes. Herein, we review the intersection between Hsps and the insulin/IGF systems under normal and pathological conditions. The discussion will emphasize the potential of non-toxic HSR inducers as viable therapeutic agents.
authors.affiliation: Neuroscience Graduate Program, The University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Urban
authors.forename: Rick T
authors.initials: RT
authors.lastname: Dobrowsky
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
mesh_terms: D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: D006360:Heat-Shock Proteins; D007328:Insulin; D007334:Insulin-Like Growth Factor I