title: Stressing Out Hsp90 in Neurotoxic Proteinopathies.
abstract: A toxic accumulation of proteins is the hallmark pathology of several neurodegenerative disorders. Protein accumulation is regularly prevented by the network of molecular chaperone proteins, including and especially Hsp90. For reasons not yet elucidated, Hsp90 and the molecular chaperones interact with, but do not degrade, these toxic proteins resulting in the pathogenic accumulation of proteins such as tau, in Alzheimer's Disease, and α-synuclein, in Parkinson's Disease. In this review, we describe the associations between Hsp90 and the pathogenic and driver proteins of several neurodegenerative disorders. We additionally describe how the inhibition of Hsp90 promotes the degradation of both mutant and pathogenic protein species in models of neurodegenerative diseases. We also examine the current state of Hsp90 inhibitors capable of crossing the blood-brain barrier; compounds which may be capable of slowing, preventing, and possible reversing neurodegenerative diseases.
authors.forename: Carmen
authors.initials: C
authors.lastname: Inda
authors.forename: Alexander
authors.initials: A
authors.lastname: Bolaender
authors.forename: Tai
authors.initials: T
authors.lastname: Wang
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Gandu
authors.affiliation: Program in Chemical Biology, Memorial Sloan-Kettering Cancer Center, New York, USA. korenj@mskcc.org.
authors.forename: John
authors.initials: J
authors.lastname: Koren
mesh_terms: D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D016875:tau Proteins