Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

Xiumei Wu; Mengyun Xu; Mengya Geng; Shuo Chen; Peter J Little; Suowen Xu; Jianping Weng

doi:10.1038/s41392-023-01439-y

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Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

Journal article

Open access

Peer reviewed

Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

Xiumei Wu, Mengyun Xu, Mengya Geng, Shuo Chen, Peter J Little, Suowen Xu and Jianping Weng

Signal Transduction and Targeted Therapy, Vol.8(1), pp.1-45

2023

DOI: https://doi.org/10.1038/s41392-023-01439-y

PMCID: PMC10224996

PMID: 37244925

Appears in UniSC Diversity and Inclusion Research Collection

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Abstract

Metabolic disorders

Biochemistry

UniSC Diversity Area - Disability and Inclusion

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. The most common form of NCD is metabolic diseases, which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum. Protein posttranslational modification (PTM) is an important term that refers to biochemical modification of specific amino acid residues in target proteins, which immensely increases the functional diversity of the proteome. The range of PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, and several novel PTMs. Here, we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences, including diabetes, obesity, fatty liver diseases, hyperlipidemia, and atherosclerosis. Building upon this framework, we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications, showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials, and offer future perspectives. Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.

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Title: Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies
Authors: Xiumei Wu (Author) - University of Science and Technology of China
Mengyun Xu (Author) - University of Science and Technology of China
Mengya Geng (Author) - University of Science and Technology of China
Shuo Chen (Author) - University of Science and Technology of China
Peter J Little (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
Suowen Xu (Author) - University of Science and Technology of China
Jianping Weng (Corresponding Author) - University of Science and Technology of China
Publication details: Signal Transduction and Targeted Therapy, Vol.8(1), pp.1-45
Publisher: Nature Publishing Group
Date published: 2023
DOI: 10.1038/s41392-023-01439-y
ISSN: 2059-3635
PMID: 37244925; PMC10224996
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Grant note: 2021YFC2500500/ National Key R&D Program of China 82070464, 81941022, 81530025/ National Natural Science Foundation of China XDB38010100/ Strategic Priority Research Program of the Chinese Academy of Sciences CXGG02/ The First Affiliated Hospital of USTC 202104j07020051/ Anhui Provincial Key Research and Development Program 2208085J08/ Anhui Provincial Natural Science Foundation 2017BT01S131/ Guangdong Pearl River Talents Program
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99730498702621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology

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