High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies
High Mobility Group Box 1 (HMGB1) is a highly conserved non-histone chromatin-associated protein across species, primarily recognized for its regulatory impact on vital cellular processes, like autophagy, cell survival, and apoptosis. HMGB1 exhibits dual functionality based on its localization: both...
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2024-11-01
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| author | Sayantap Datta Mohammad Atiqur Rahman Saisudha Koka Krishna M. Boini |
| author_facet | Sayantap Datta Mohammad Atiqur Rahman Saisudha Koka Krishna M. Boini |
| author_sort | Sayantap Datta |
| collection | DOAJ |
| description | High Mobility Group Box 1 (HMGB1) is a highly conserved non-histone chromatin-associated protein across species, primarily recognized for its regulatory impact on vital cellular processes, like autophagy, cell survival, and apoptosis. HMGB1 exhibits dual functionality based on its localization: both as a non-histone protein in the nucleus and as an inducer of inflammatory cytokines upon extracellular release. Pathophysiological insights reveal that HMGB1 plays a significant role in the onset and progression of a vast array of diseases, viz., atherosclerosis, kidney damage, cancer, and neurodegeneration. However, a clear mechanistic understanding of HMGB1 release, translocation, and associated signaling cascades in mediating such physiological dysfunctions remains obscure. This review presents a detailed outline of HMGB1 structure–function relationship and its regulatory role in disease onset and progression from a signaling perspective. This review also presents an insight into the status of HMGB1 druggability, potential limitations in understanding HMGB1 pathophysiology, and future perspective of studies that can be undertaken to address the existing scientific gap. Based on existing paradigm of various studies, HMGB1 is a critical regulator of inflammatory cascades and drives the onset and progression of a broad spectrum of dysfunctions. Studies focusing on HMGB1 druggability have enabled the development of biologics with potential clinical benefits. However, deeper understanding of post-translational modifications, redox states, translocation mechanisms, and mitochondrial interactions can potentially enable the development of better courses of therapy against HMGB1-mediated physiological dysfunctions. |
| format | Article |
| id | doaj-art-67f714c19332410aafb2f7e6b1ca35ee |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-67f714c19332410aafb2f7e6b1ca35ee2025-08-20T02:50:18ZengMDPI AGCells2073-44092024-11-011323194610.3390/cells13231946High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic StrategiesSayantap Datta0Mohammad Atiqur Rahman1Saisudha Koka2Krishna M. Boini3Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USADepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USADepartment of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USADepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USAHigh Mobility Group Box 1 (HMGB1) is a highly conserved non-histone chromatin-associated protein across species, primarily recognized for its regulatory impact on vital cellular processes, like autophagy, cell survival, and apoptosis. HMGB1 exhibits dual functionality based on its localization: both as a non-histone protein in the nucleus and as an inducer of inflammatory cytokines upon extracellular release. Pathophysiological insights reveal that HMGB1 plays a significant role in the onset and progression of a vast array of diseases, viz., atherosclerosis, kidney damage, cancer, and neurodegeneration. However, a clear mechanistic understanding of HMGB1 release, translocation, and associated signaling cascades in mediating such physiological dysfunctions remains obscure. This review presents a detailed outline of HMGB1 structure–function relationship and its regulatory role in disease onset and progression from a signaling perspective. This review also presents an insight into the status of HMGB1 druggability, potential limitations in understanding HMGB1 pathophysiology, and future perspective of studies that can be undertaken to address the existing scientific gap. Based on existing paradigm of various studies, HMGB1 is a critical regulator of inflammatory cascades and drives the onset and progression of a broad spectrum of dysfunctions. Studies focusing on HMGB1 druggability have enabled the development of biologics with potential clinical benefits. However, deeper understanding of post-translational modifications, redox states, translocation mechanisms, and mitochondrial interactions can potentially enable the development of better courses of therapy against HMGB1-mediated physiological dysfunctions.https://www.mdpi.com/2073-4409/13/23/1946HMGB1cardiovascular diseasesrenal dysfunctionreceptor for advanced glycation end products (RAGE) |
| spellingShingle | Sayantap Datta Mohammad Atiqur Rahman Saisudha Koka Krishna M. Boini High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies Cells HMGB1 cardiovascular diseases renal dysfunction receptor for advanced glycation end products (RAGE) |
| title | High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies |
| title_full | High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies |
| title_fullStr | High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies |
| title_full_unstemmed | High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies |
| title_short | High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies |
| title_sort | high mobility group box 1 hmgb1 molecular signaling and potential therapeutic strategies |
| topic | HMGB1 cardiovascular diseases renal dysfunction receptor for advanced glycation end products (RAGE) |
| url | https://www.mdpi.com/2073-4409/13/23/1946 |
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