Dear Editor:Geldanamycin is a benzoquinone ansamycin,which wasoriginally described as a tyrosine kinase inhibitor.How-ever,subsequent studies have revealed that geldanamycinbinds to and inhibits heat-shock protein 90(Hsp90)activity[1].Hsp90 is a molecular chaperone involved in the con-formational maturation of proteins such as mutated p53,Raf-1,Akt,Bcr-Ab1,and ErbB2.It is suggested that agentsinhibiting Hsp90 have anti-cancer properties,although theprecise molecular mechanisms underlying the anti-cancereffects of geldanamycin are not well understood.Increasing evidence has suggested that diabetes andneurodegenerative disorders such as Parkinson’s andAlzheimer’s diseases are related to the disruption ofendoplasmic reticulum(ER)function.In response to ERstress,unfolded proteins accumulate and aggregate in theER,which will trigger many rescuer responses,includingthe unfolded protein response(UPR)and ER-associateddegradation.Interestingly,geldanamycin has been shownto upregulate ER chaperones and the expression of CHOP[2].Moreover,Hsp90 associates with PERK and IRE1α,ER-resident trans-membrane protein kinases involved inER stress response[3].These observations suggest that Dear Editor: Geldanamycin is a benzoquinone ansamycin, which was orbitally described as a tyrosine kinase inhibitor. How-ever, subsequent studies have revealed that geldanamycinbinds to and inhibits heat-shock protein 90 (Hsp90) activity [1]. Hsp90 is a molecular chaperone involved in the con-formational maturation of proteins such as mutated p53, Raf-1, Akt, Bcr-Abl, and ErbB2.It is suggested that these agents inhibit Hsp90 have anti-cancer properties, although theprecise molecular mechanisms underlying the anti-cancereffects of geldanamycin are not well understood. Increasing evidence has shown that diabetes and neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases are related to the disruption of endoplasmic reticulum (ER) function. In response to ERstress, unfolded proteins accumulate and aggregate in the ER, which will trigger many rescuer responses, includingthe unfolded protein response (UPR) and ER-associated degradation. Uniquely, geldanamycin has been shownto upregulate ER chapero nes and the expression of CHOP [2]. Moreover, Hsp90 associates with PERK and IRE1α, ER-resident trans-membrane protein kinases involved in ER stress response [3]. These observations suggest that