Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies
Abstract 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 complicatio...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-05-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-023-01439-y |
| _version_ | 1797817799959117824 |
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| author | Xiumei Wu Mengyun Xu Mengya Geng Shuo Chen Peter J. Little Suowen Xu Jianping Weng |
| author_facet | Xiumei Wu Mengyun Xu Mengya Geng Shuo Chen Peter J. Little Suowen Xu Jianping Weng |
| author_sort | Xiumei Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T08:58:50Z |
| format | Article |
| id | doaj.art-cbb0e4d1b8c74c47b177fcfbcfc22eb6 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-03-13T08:58:50Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-cbb0e4d1b8c74c47b177fcfbcfc22eb62023-05-28T11:28:47ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352023-05-018114510.1038/s41392-023-01439-yTargeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapiesXiumei Wu0Mengyun Xu1Mengya Geng2Shuo Chen3Peter J. Little4Suowen Xu5Jianping Weng6Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of ChinaDepartment of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of ChinaDepartment of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of ChinaDepartment of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of ChinaSchool of Pharmacy, University of Queensland, Pharmacy Australia Centre of ExcellenceDepartment of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of ChinaDepartment of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of ChinaAbstract 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.https://doi.org/10.1038/s41392-023-01439-y |
| spellingShingle | Xiumei Wu Mengyun Xu Mengya Geng Shuo Chen Peter J. Little Suowen Xu Jianping Weng Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies Signal Transduction and Targeted Therapy |
| title | Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies |
| title_full | Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies |
| title_fullStr | Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies |
| title_full_unstemmed | Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies |
| title_short | Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies |
| title_sort | targeting protein modifications in metabolic diseases molecular mechanisms and targeted therapies |
| url | https://doi.org/10.1038/s41392-023-01439-y |
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