Targeting the Diabetic Chaperome to Improve Peripheral Neuropathy.
Authors Dobrowsky RT
Submitted By Rick Dobrowsky on 8/1/2016
Status Published
Journal Current diabetes reports
Year 2016
Date Published 8/1/2016
Volume : Pages 16 : 71
PubMed Reference 27318486
Abstract The chaperome constitutes a broad family of molecular chaperones and
co-chaperones that facilitate the folding, refolding, and degradation of the
proteome. Heat shock protein 90 (Hsp90) promotes the folding of numerous
oncoproteins to aid survival of malignant phenotypes, and small molecule
inhibitors of the Hsp90 chaperone complex offer a viable approach to treat
certain cancers. One therapeutic attribute of this approach is the selectivity
of these molecules to target high affinity oncogenic Hsp90 complexes present in
tumor cells, which are absent in nontransformed cells. This selectivity has
given rise to the idea that disease may contribute to forming a stress chaperome
that is functionally distinct in its ability to interact with small molecule
Hsp90 modulators. Consistent with this premise, modulating Hsp90 improves
clinically relevant endpoints of diabetic peripheral neuropathy but has little
impact in nondiabetic nerve. The concept of targeting the "diabetic chaperome"
to treat diabetes and its complications is discussed.