TY - JOUR
T1 - Ubiquitin-proteasome system in diabetic retinopathy
AU - Svikle, Zane
AU - Peterfelde, Beate
AU - Sjakste, Nikolajs
AU - Baumane, Kristine
AU - Verkauskiene, Rasa
AU - Jeng, Chi Juei
AU - Sokolovska, Jelizaveta
N1 - Funding Information:
The work was supported by the project of the Mutual funds Taiwan-Latvia-Lithuania “Novel biomarkers of diabetic retinopathy: epigenetic modifications of genes of ubiquitin-proteasome system, telomere length and proteasome concentration” and a fundamental research grant in Biomedicine and Pharmacy “Research of biomarkers and natural substances for acute and chronic diseases’ diagnostics and personalized treatment” by the Faculty of Medicine, University of Latvia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
The following grant information was disclosed by the authors: Mutual Funds Taiwan-Latvia-Lithuania. Biomedicine and Pharmacy, Faculty of Medicine, University of Latvia.
Funding Information:
Zane Svikle, Beate Peterfelde, Nikolajs Sjakste, Kristine Baumane, Rasa Verkauskiene, and Chi-Juei Jeng report no conflicts of interest. Jelizaveta Sokolovska reports lecture fees and educational grants from Sandoz, Sanofi, MSD, NovoNordisc, AstraZeneca, Grindex outside the submitted work. Nikolajs Sjakste is an Academic Editor for PeerJ.
Funding Information:
The work was supported by the project of the Mutual funds Taiwan-Latvia-Lithuania “Novel biomarkers of diabetic retinopathy: epigenetic modifications of genes of ubiquitin-proteasome system, telomere length and proteasome concentration” and a fundamental research grant in Biomedicine and Pharmacy “Research of biomarkers and natural substances for acute and chronic diseases' diagnostics and personalized treatment” by the Faculty of Medicine, University of Latvia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The following grant information was disclosed by the authors: Mutual Funds Taiwan-Latvia-Lithuania. Biomedicine and Pharmacy, Faculty of Medicine, University of Latvia.
Publisher Copyright:
© Copyright 2022 Svikle et al.
PY - 2022/7
Y1 - 2022/7
N2 - Diabetic retinopathy (DR) is the most common complication of diabetes, being the most prevalent reason for blindness among the working-age population in the developed world. Despite constant improvement of understanding of the pathogenesis of DR, identification of novel biomarkers of DR is needed for improvement of patient risk stratification and development of novel prevention and therapeutic approaches. The ubiquitin-proteasome system (UPS) is the primary protein quality control system responsible for recognizing and degrading of damaged proteins. This review aims to summarize literature data on modifications of UPS in diabetes and DR. First, we briefly review the structure and functions of UPS in physiological conditions. We then describe how UPS is involved in the development and progression of diabetes and touch upon the association of UPS genetic factors with diabetes and its complications. Further, we focused on the effect of diabetes-induced hyperglycemia, oxidative stress and hypoxia on UPS functioning, with examples of studies on DR. In other sections, we discussed the association of several other mechanisms of DR (endoplasmic reticulum stress, neurodegeneration etc) with UPS modifications. Finally, UPS-affecting drugs and remedies are reviewed. This review highlights UPS as a promising target for the development of therapies for DR prevention and treatment and identifies gaps in existing knowledge and possible future study directions.
AB - Diabetic retinopathy (DR) is the most common complication of diabetes, being the most prevalent reason for blindness among the working-age population in the developed world. Despite constant improvement of understanding of the pathogenesis of DR, identification of novel biomarkers of DR is needed for improvement of patient risk stratification and development of novel prevention and therapeutic approaches. The ubiquitin-proteasome system (UPS) is the primary protein quality control system responsible for recognizing and degrading of damaged proteins. This review aims to summarize literature data on modifications of UPS in diabetes and DR. First, we briefly review the structure and functions of UPS in physiological conditions. We then describe how UPS is involved in the development and progression of diabetes and touch upon the association of UPS genetic factors with diabetes and its complications. Further, we focused on the effect of diabetes-induced hyperglycemia, oxidative stress and hypoxia on UPS functioning, with examples of studies on DR. In other sections, we discussed the association of several other mechanisms of DR (endoplasmic reticulum stress, neurodegeneration etc) with UPS modifications. Finally, UPS-affecting drugs and remedies are reviewed. This review highlights UPS as a promising target for the development of therapies for DR prevention and treatment and identifies gaps in existing knowledge and possible future study directions.
KW - Diabetes
KW - Diabetic eye disease
KW - Retinopathy
KW - Ubiquitin-proteasome system
UR - http://www.scopus.com/inward/record.url?scp=85135055430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85135055430&partnerID=8YFLogxK
U2 - 10.7717/peerj.13715
DO - 10.7717/peerj.13715
M3 - Article
AN - SCOPUS:85135055430
SN - 2167-8359
VL - 10
JO - PeerJ
JF - PeerJ
M1 - e13715
ER -
