Protein stability and degradation in health and disease

Lene Clausen, Amanda Bering Abildgaard, Sarah K. Gersing, Amelie Stein, Kresten Lindorff-Larsen*, Rasmus Hartmann-Petersen

*Corresponding author af dette arbejde
8 Citationer (Scopus)

Abstract

The cellular proteome performs highly varied functions to sustain life. Since most of these functions require proteins to fold properly, they can be impaired by mutations that affect protein structure, leading to diseases such as Alzheimer's disease, cystic fibrosis, and Lynch syndrome. The cell has evolved an intricate protein quality control (PQC) system that includes degradation pathways and a multitude of molecular chaperones and co-chaperones, all working together to catalyze the refolding or removal of aberrant proteins. Thus, the PQC system limits the harmful consequences of dysfunctional proteins, including those arising from disease-causing mutations. This complex system is still not fully understood. In particular the structural and sequence motifs that, when exposed, trigger degradation of misfolded proteins are currently under investigation. Moreover, several attempts are being made to activate or inhibit parts of the PQC system as a treatment for diseases. Here, we briefly review the present knowledge on the PQC system and list current strategies that are employed to exploit the system in disease treatment.

OriginalsprogEngelsk
TitelMolecular Chaperones in Human Disorders
RedaktørerRossen Donev
ForlagAcademic Press
Publikationsdato1 jan. 2019
Sider61-83
Kapitel2
ISBN (Trykt)978-0-12-815557-8
DOI
StatusUdgivet - 1 jan. 2019
NavnAdvances in Protein Chemistry and Structural Biology
Vol/bind114
ISSN1876-1623

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