17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration

Pratt, W.B. & Toft, D.O. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp. Biol. Med. (Maywood) 228, 111–133 (2003).

Neckers, L., Schulte, T.W. & Mimnaugh, E. Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest. New Drugs 17, 361–373 (1999).

Supko, J.G., Hickman, R.L., Grever, M.R. & Malspeis, L. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol. 36, 305–315 (1995).

Schulte, T.W. & Neckers, L.M. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. 42, 273–279 (1998).

Page, J. et al. Comparison of geldanamycin (NSC-122750) and 17-allylaminogeldanamycin (NSC-330507D) toxicity in rats. Proc. Am. Assoc. Cancer Res. 38, 308 (1997).

Sullivan, W. et al. Nucleotides and two functional states of hsp90. J. Biol. Chem. 272, 8007–8012 (1997).

Bagatell, R. et al. Destabilization of steroid receptors by heat shock protein 90-binding drugs: a ligand-independent approach to hormonal therapy of breast cancer. Clin. Cancer Res. 7, 2076–2084 (2001).

Neckers, L. Heat shock protein 90 inhibition by 17-allylamino-17-demethoxygeldanamycin: a novel therapeutic approach for treating hormone-refractory prostate cancer. Clin. Cancer Res. 8, 962–966 (2002).

Felts, S.J. & Toft, D.O. p23, a simple protein with complex activities. Cell Stress Chaperones 8, 108–113 (2003).

Johnson, J.L. & Toft, D.O. Binding of p23 and hsp90 during assembly with the progesterone receptor. Mol. Endocrinol. 9, 670–678 (1995).

Smith, D.F. et al. Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent. Mol. Cell. Biol. 15, 6804–6812 (1995).

Whitesell, L. & Cook, P. Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Mol. Endocrinol. 10, 705–712 (1996).

Schneider, C. et al. Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc. Natl. Acad. Sci. USA 93, 14536–14541 (1996).

Solit, D.B. et al. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin. Cancer Res. 8, 986–993 (2002).

Vanaja, D.K., Mitchell, S.H., Toft, D.O. & Young, C.Y. Effect of geldanamycin on androgen receptor function and stability. Cell Stress Chaperones 7, 55–64 (2002).

Beliakoff, J. et al. Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors. Clin. Cancer Res. 9, 4961–4971 (2003).

Bonvini, P., Dalla Rosa, H., Vignes, N. & Rosolen, A. Ubiquitination and proteasomal degradation of nucleophosmin-anaplastic lymphoma kinase induced by 17-allylamino-demethoxygeldanamycin: role of the co-chaperone carboxyl heat shock protein 70-interacting protein. Cancer Res. 64, 3256–3264 (2004).

Mimnaugh, E.G., Chavany, C. & Neckers, L. Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J. Biol. Chem. 271, 22796–22801 (1996).

Kamal, A. et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425, 407–410 (2003).

Whitesell, L., Bagatell, R. & Falsey, R. The stress response: implications for the clinical development of hsp90 inhibitors. Curr. Cancer Drug Targets 3, 349–358 (2003).

Muchowski, P.J. & Wacker, J.L. Modulation of neurodegeneration by molecular chaperones. Nat. Rev. Neurosci. 6, 11–22 (2005).

Sittler, A. et al. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet. 10, 1307–1315 (2001).

Hay, D.G. et al. Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach. Hum. Mol. Genet. 13, 1389–1405 (2004).

Auluck, P.K. & Bonini, N.M. Pharmacological prevention of Parkinson disease in Drosophila . Nat. Med. 8, 1185–1186 (2002).

Dou, F. et al. Chaperones increase association of tau protein with microtubules. Proc. Natl. Acad. Sci. USA 100, 721–726 (2003).

Petrucelli, L. et al. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. Hum. Mol. Genet. 13, 703–714 (2004).

Lu, A., Ran, R., Parmentier-Batteur, S., Nee, A. & Sharp, F.R. Geldanamycin induces heat shock proteins in brain and protects against focal cerebral ischemia. J. Neurochem. 81, 355–364 (2002).

Murphy, P. et al. Suppressive effects of ansamycins on inducible nitric oxide synthase expression and the development of experimental autoimmune encephalomyelitis. J. Neurosci. Res. 67, 461–470 (2002).

La Spada, A.R., Wilson, E.M., Lubahn, D.B., Harding, A.E. & Fischbeck, K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991).

Sobue, G. et al. X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain 112, 209–232 (1989).

Zoghbi, H.Y. & Orr, H.T. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23, 217–247 (2000).

Tanaka, F. et al. Founder effect in spinal and bulbar muscular atrophy (SBMA). Hum. Mol. Genet. 5, 1253–1257 (1996).

Doyu, M. et al. Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene. Ann. Neurol. 32, 707–710 (1992).

Adachi, H. et al. Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain 128, 659–670 (2005).

Katsuno, M. et al. Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron 35, 843–854 (2002).

Adachi, H. et al. Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. J. Neurosci. 23, 2203–2211 (2003).

Katsuno, M. et al. Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat. Med. 9, 768–773 (2003).

Minamiyama, M. et al. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 13, 1183–1192 (2004).

Bailey, C.K., Andriola, I.F., Kampinga, H.H. & Merry, D.E. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 11, 515–523 (2002).

Lieberman, A.P., Harmison, G., Strand, A.D., Olson, J.M. & Fischbeck, K.H. Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor. Hum. Mol. Genet. 11, 1967–1976 (2002).

Zou, J., Guo, Y., Guettouche, T., Smith, D.F. & Voellmy, R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94, 471–480 (1998).

Egorin, M.J. et al. Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1. Cancer Chemother. Pharmacol. 47, 291–302 (2001).

Ravikumar, B. et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36, 585–595 (2004).

Ferrante, R.J. et al. Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease. J. Neurosci. 24, 10335–10342 (2004).

Cummings, C.J. et al. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat. Genet. 19, 148–154 (1998).

Kobayashi, Y. et al. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. J. Biol. Chem. 275, 8772–8778 (2000).

Blagosklonny, M.V., Toretsky, J., Bohen, S. & Neckers, L. Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90. Proc. Natl. Acad. Sci. USA 93, 8379–8383 (1996).

Yamamoto, A., Lucas, J.J. & Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101, 57–66 (2000).

Xia, H. et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med. 10, 816–820 (2004).

Ishigaki, S. et al. X-Linked inhibitor of apoptosis protein is involved in mutant SOD1-mediated neuronal degeneration. J. Neurochem. 82, 576–584 (2002).