摘要
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,ADPribosylation,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.
基金
supported by grants from the National Key R&D Program of China(Grant No.2021YFC2500500)
the National Natural Science Foundation of China(Grant Nos.82070464,81941022,81530025)
the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB38010100)
supported by Program for Innovative Research Team of The First Affliated Hospital of USTC(CXGG02)
Anhui Provincial Key Research and Development Program(Grant No.202104j07020051)
Anhui Provincial Natural Science Foundation(Grant No.2208085J08)
Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant No.2017BT01S131)。
