Therapeutic approaches targeting proteostasis in kidney disease and fibrosis
Journal
International Journal of Molecular Sciences
Journal Volume
22
Journal Issue
16
Date Issued
2021
Author(s)
Abstract
Pathological insults usually disturb the folding capacity of cellular proteins and lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which leads to so-called “ER stress”. Increasing evidence indicates that ER stress acts as a trigger factor for the development and progression of many kidney diseases. The unfolded protein responses (UPRs), a set of molecular signals that resume proteostasis under ER stress, are thought to restore the adaptive process in chronic kidney disease (CKD) and renal fibrosis. Furthermore, the idea of targeting UPRs for CKD treatment has been well discussed in the past decade. This review summarizes the up-to-date liter-ature regarding studies on the relationship between the UPRs, systemic fibrosis, and renal diseases. We also address the potential therapeutic possibilities of renal diseases based on the modulation of UPRs and ER proteostasis. Finally, we list some of the current UPR modulators and their therapeutic potentials. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Endoplasmic reticulum stress; Fibrosis; Kidney; Proteostasis; Unfolded protein responses
SDGs
Other Subjects
chronic kidney failure; drug effect; endoplasmic reticulum; endoplasmic reticulum stress; fibrosis; human; metabolism; molecular library; molecularly targeted therapy; pathology; pharmacology; protein homeostasis; signal transduction; unfolded protein response; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Fibrosis; Humans; Molecular Targeted Therapy; Proteostasis; Renal Insufficiency, Chronic; Signal Transduction; Small Molecule Libraries; Unfolded Protein Response
Publisher
MDPI AG
Type
review