Heat shock protein 90: translation from cancer to Alzheimer's disease treatment?
Both malignant transformation and neurodegeneration, as it occurs in Alzheimer's disease, are complex and lengthy multistep processes characterized by abnormal expression, post-translational modification, and processing of certain proteins. To maintain and allow the accumulation of these dysregulated processes, and to facilitate the step-wise evolution of the disease phenotype, cells must co-opt a compensatory regulatory mechanism. In cancer, this role has been attributed to heat shock protein 90 (Hsp90), a molecular chaperone that maintains the functional conformation of multiple proteins involved in cell-specific oncogenic processes. In this sense, at the phenotypic level, Hsp90 appears to serve as a biochemical buffer for the numerous cancer-specific lesions that are characteristic of diverse tumors. The current review proposes a similar role for Hsp90 in neurodegeneration. It will present experimentally demonstrated, but also hypothetical, roles that suggest Hsp90 can act as a regulator of pathogenic changes that lead to the neurodegenerative phenotype in Alzheimer's disease.
Luo
Wenjie
W
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University and Fisher Foundation for Alzheimer's Disease, New York, NY 10021, USA. luow@rockefeller.edu
Rodina
Anna
A
Chiosis
Gabriela
G
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D016229:Amyloid beta-Peptides; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones