Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease
Non-alcoholic fatty liver (NAFL) is the most common chronic liver disease. Activation of mitogen-activated kinases (MAPK) cascade, which leads to c-Jun N-terminal kinase (JNK) activation occurs in the liver in response to the nutritional and metabolic stress. The aberrant activation of MAPKs, especi...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/2035 |
| _version_ | 1797432345366626304 |
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| author | Robert W. M. Min Filbert W. M. Aung Bryant Liu Aliza Arya Sanda Win |
| author_facet | Robert W. M. Min Filbert W. M. Aung Bryant Liu Aliza Arya Sanda Win |
| author_sort | Robert W. M. Min |
| collection | DOAJ |
| description | Non-alcoholic fatty liver (NAFL) is the most common chronic liver disease. Activation of mitogen-activated kinases (MAPK) cascade, which leads to c-Jun N-terminal kinase (JNK) activation occurs in the liver in response to the nutritional and metabolic stress. The aberrant activation of MAPKs, especially c-Jun-N-terminal kinases (JNKs), leads to unwanted genetic and epi-genetic modifications in addition to the metabolic stress adaptation in hepatocytes. A mechanism of sustained P-JNK activation was identified in acute and chronic liver diseases, suggesting an important role of aberrant JNK activation in NASH. Therefore, modulation of JNK activation, rather than targeting JNK protein levels, is a plausible therapeutic application for the treatment of chronic liver disease. |
| first_indexed | 2024-03-09T10:00:09Z |
| format | Article |
| id | doaj.art-1add24cfb7484ffe81006f19d5caa39f |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:00:09Z |
| publishDate | 2022-08-01 |
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| series | Biomedicines |
| spelling | doaj.art-1add24cfb7484ffe81006f19d5caa39f2023-12-01T23:29:37ZengMDPI AGBiomedicines2227-90592022-08-01108203510.3390/biomedicines10082035Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver DiseaseRobert W. M. Min0Filbert W. M. Aung1Bryant Liu2Aliza Arya3Sanda Win4Rush Medical College, Rush University, Chicago, IL 60612, USABrown University, Providence, RI 02912, USADivision of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Ave., HMR 612, Los Angeles, CA 90089, USADivision of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Ave., HMR 612, Los Angeles, CA 90089, USADivision of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Ave., HMR 612, Los Angeles, CA 90089, USANon-alcoholic fatty liver (NAFL) is the most common chronic liver disease. Activation of mitogen-activated kinases (MAPK) cascade, which leads to c-Jun N-terminal kinase (JNK) activation occurs in the liver in response to the nutritional and metabolic stress. The aberrant activation of MAPKs, especially c-Jun-N-terminal kinases (JNKs), leads to unwanted genetic and epi-genetic modifications in addition to the metabolic stress adaptation in hepatocytes. A mechanism of sustained P-JNK activation was identified in acute and chronic liver diseases, suggesting an important role of aberrant JNK activation in NASH. Therefore, modulation of JNK activation, rather than targeting JNK protein levels, is a plausible therapeutic application for the treatment of chronic liver disease.https://www.mdpi.com/2227-9059/10/8/2035JNKSABJNK activation loopROSMAP kinase cascadedrug therapy |
| spellingShingle | Robert W. M. Min Filbert W. M. Aung Bryant Liu Aliza Arya Sanda Win Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease Biomedicines JNK SAB JNK activation loop ROS MAP kinase cascade drug therapy |
| title | Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease |
| title_full | Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease |
| title_fullStr | Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease |
| title_full_unstemmed | Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease |
| title_short | Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease |
| title_sort | mechanism and therapeutic targets of c jun n terminal kinases activation in nonalcoholic fatty liver disease |
| topic | JNK SAB JNK activation loop ROS MAP kinase cascade drug therapy |
| url | https://www.mdpi.com/2227-9059/10/8/2035 |
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