Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Protein Homeostasis as a Therapeutic Target for Diseases of Protein Conformation

Author(s): Barbara Calamini and Richard I. Morimoto

Volume 12, Issue 22, 2012

Page: [2623 - 2640] Pages: 18

DOI: 10.2174/1568026611212220014

Price: $65

Abstract

Protein misfolding and aggregation are widely implicated in an increasing number of human diseases providing for new therapeutic opportunities targeting protein homeostasis (proteostasis). The cellular response to proteotoxicity is highly regulated by stress signaling pathways, molecular chaperones, transport and clearance machineries that function as a proteostasis network (PN) to protect the stability and functional properties of the proteome. Consequently, the PN is essential at the cellular and organismal level for development and lifespan. However, when challenged during aging, stress, and disease, the folding and clearance machineries can become compromised leading to both gain-of-function and loss-offunction proteinopathies. Here, we assess the role of small molecules that activate the heat shock response, the unfolded protein response, and clearance mechanisms to increase PN capacity and protect cellular proteostasis against proteotoxicity. We propose that this strategy to enhance cell stress pathways and chaperone activity establishes a cytoprotective state against misfolding and/or aggregation and represents a promising therapeutic avenue to prevent the cellular damage associated with the variety of protein conformational diseases.

Keywords: Protein conformational diseases, proteostasis network, proteostasis regulators, stress responses

« Previous

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy