title: Hsp90 as a Potential Therapeutic Target in Retinal Disease.
abstract: The molecular chaperone heat shock protein 90 (Hsp90) is a pivotal cellular regulator involved in the folding, activation and assembly of a wide range of proteins. Hsp90 has multiple roles in the retina and the use of different Hsp90 inhibitors has been shown to prevent retinal degeneration in models of retinitis pigmentosa and age-related macular degeneration. Hsp90 is also a potential target in uveal melanoma. Mechanistically, Hsp90 inhibition can evoke a dual response in the retina; stimulating a stress response with molecular chaperone expression. Thereby leading to an improvement in visual function and photoreceptor survival; however, prolonged inhibition can also stimulate the degradation of Hsp90 client proteins potentially deleteriously affect vision. Here, we review the multiple roles of Hsp90 in the retina and the therapeutic potential of Hsp90 as a target.
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, 11-43 Bath Street, EC1V 9EL, London, UK. m.aguila@ucl.ac.uk.
authors.forename: Mònica
authors.initials: M
authors.lastname: Aguilà
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, 11-43 Bath Street, EC1V 9EL, London, UK. m.cheetham@ucl.ac.uk.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cheetham
mesh_terms: D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D011728:Pyridones / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000188:drug therapy / Q000378:metabolism; D014785:Vision, Ocular / Q000187:drug effects
chemical_list: C570862:2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D011728:Pyridones; D011743:Pyrimidines
keywords: AMD; Hsp90; Hsp90 inhibition; Molecular chaperones; RP; Retinal degeneration; Uveal melanoma