Pathways of Cellular Proteostasis in Aging and Disease

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2017 Nov 12

PMID 29127110

Citations 356

Authors

Courtney L Klaips

Gopal Gunanathan Jayaraj

F Ulrich Hartl

Affiliations

Soon will be listed here.

Abstract

Ensuring cellular protein homeostasis, or proteostasis, requires precise control of protein synthesis, folding, conformational maintenance, and degradation. A complex and adaptive proteostasis network coordinates these processes with molecular chaperones of different classes and their regulators functioning as major players. This network serves to ensure that cells have the proteins they need while minimizing misfolding or aggregation events that are hallmarks of age-associated proteinopathies, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. It is now clear that the capacity of cells to maintain proteostasis undergoes a decline during aging, rendering the organism susceptible to these pathologies. Here we discuss the major proteostasis pathways in light of recent research suggesting that their age-dependent failure can both contribute to and result from disease. We consider different strategies to modulate proteostasis capacity, which may help develop urgently needed therapies for neurodegeneration and other age-dependent pathologies.

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