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.
Keywords: HsP90, Neurodegenerative disease, α-Synuclein, DNA.
Current Topics in Medicinal Chemistry
Title:Stressing Out Hsp90 in Neurotoxic Proteinopathies
Volume: 16 Issue: 25
Author(s): Carmen Inda, Alexander Bolaender, Tai Wang, Srinivasa R. Gandu and John Koren III
Affiliation:
Keywords: HsP90, Neurodegenerative disease, α-Synuclein, DNA.
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.
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Cite this article as:
Inda Carmen, Bolaender Alexander, Wang Tai, Gandu R. Srinivasa and III Koren John, Stressing Out Hsp90 in Neurotoxic Proteinopathies, Current Topics in Medicinal Chemistry 2016; 16 (25) . https://dx.doi.org/10.2174/1568026616666160413141350
DOI https://dx.doi.org/10.2174/1568026616666160413141350 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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