Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?

Abstract

Protein homeostasis (proteostasis), the correct balance between production and degradation of proteins, is essential for the health and survival of cells. Proteostasis requires an intricate network of protein quality control pathways (the proteostasis network) that work to prevent protein aggregation and maintain proteome health throughout the lifespan of the cell. Collapse of proteostasis has been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disorder. Here, we review the evidence linking dysfunctional proteostasis to the etiology of ALS and discuss how ALS-associated insults affect the proteostasis network. Finally, we discuss the potential therapeutic benefit of proteostasis network modulation in ALS.

Metadata

Authors/Creators:

Webster, C.
Smith, E.
Shaw, P.
De Vos, K. https://orcid.org/0000-0003-2161-6309

© 2017 Webster, Smith, Shaw and De Vos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Keywords:

protein homeostasis; protein aggregation; amyotrophic lateral sclerosis (ALS); motor neuron disease; autophagy; chaperonins; unfolded protein response (UPR); proteostasis

Dates: