Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke
Diabetes mellitus, a well-established risk factor for stroke, is related to higher mortality and poorer outcomes following the stroke event. Advanced glycation end products(AGEs), their receptors RAGEs, other ligands, and several other processes contribute to the cerebrovascular pathomechanism inter...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/11/1712 |
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| author | Nivedita L. Rao Greeshma B. Kotian Jeevan K. Shetty Bhaskara P. Shelley Mackwin Kenwood Dmello Eric C. Lobo Suchetha Padar Shankar Shellette D. Almeida Saiqa R. Shah |
| author_facet | Nivedita L. Rao Greeshma B. Kotian Jeevan K. Shetty Bhaskara P. Shelley Mackwin Kenwood Dmello Eric C. Lobo Suchetha Padar Shankar Shellette D. Almeida Saiqa R. Shah |
| author_sort | Nivedita L. Rao |
| collection | DOAJ |
| description | Diabetes mellitus, a well-established risk factor for stroke, is related to higher mortality and poorer outcomes following the stroke event. Advanced glycation end products(AGEs), their receptors RAGEs, other ligands, and several other processes contribute to the cerebrovascular pathomechanism interaction in the diabetes–ischemic stroke combination. Critical reappraisal of molecular targets and therapeutic agents to mitigate them is required to identify key elements for therapeutic interventions that may improve patient outcomes. This scoping review maps evidence on the key roles of AGEs, RAGEs, other ligands such as Leukotriene B4 (LTB4), High-mobility group box 1 (HMGB1) nuclear protein, brain–kidney–muscle crosstalk, alternate pathomechanisms in neurodegeneration, and cognitive decline related to diabetic ischemic stroke. RAGE, HMGB1, nitric oxide, and polyamine mechanisms are important therapeutic targets, inflicting common consequences of neuroinflammation and oxidative stress. Experimental findings on a number of existing–emerging therapeutic agents and natural compounds against key targets are promising. The lack of large clinical trials with adequate follow-up periods is a gap that requires addressing to validate the emerging therapeutic agents. Five therapeutic components, which include agents to mitigate the AGE–RAGE axis, improved biomarkers for risk stratification, better renal dysfunction management, adjunctive anti-inflammatory–antioxidant therapies, and innovative neuromuscular stimulation for rehabilitation, are identified. A comprehensive therapeutic strategy that features all the identified components is needed for outcome improvement in diabetic stroke patients. |
| first_indexed | 2024-03-09T18:27:44Z |
| format | Article |
| id | doaj.art-c5172055bf934f518427005f4fdf2ef8 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T18:27:44Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c5172055bf934f518427005f4fdf2ef82023-11-24T07:48:11ZengMDPI AGBiomolecules2218-273X2022-11-011211171210.3390/biom12111712Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic StrokeNivedita L. Rao0Greeshma B. Kotian1Jeevan K. Shetty2Bhaskara P. Shelley3Mackwin Kenwood Dmello4Eric C. Lobo5Suchetha Padar Shankar6Shellette D. Almeida7Saiqa R. Shah8Department of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, IndiaDepartment of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, IndiaDepartment of Biochemistry, School of Medicine, Royal College of Surgeons in Ireland Medical University of Bahrain, Muharraq 228, BahrainDepartment of Neurology, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, IndiaDepartment of Public Health, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, Karnataka, IndiaDepartment of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, IndiaCollege of Physiotherapy, Dayananda Sagar University, Bangalore 560111, Karnataka, IndiaSchool of Physiotherapy, D. Y. Patil (Deemed to be University), Navi Mumbai 400706, Maharashtra, IndiaDepartment of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, IndiaDiabetes mellitus, a well-established risk factor for stroke, is related to higher mortality and poorer outcomes following the stroke event. Advanced glycation end products(AGEs), their receptors RAGEs, other ligands, and several other processes contribute to the cerebrovascular pathomechanism interaction in the diabetes–ischemic stroke combination. Critical reappraisal of molecular targets and therapeutic agents to mitigate them is required to identify key elements for therapeutic interventions that may improve patient outcomes. This scoping review maps evidence on the key roles of AGEs, RAGEs, other ligands such as Leukotriene B4 (LTB4), High-mobility group box 1 (HMGB1) nuclear protein, brain–kidney–muscle crosstalk, alternate pathomechanisms in neurodegeneration, and cognitive decline related to diabetic ischemic stroke. RAGE, HMGB1, nitric oxide, and polyamine mechanisms are important therapeutic targets, inflicting common consequences of neuroinflammation and oxidative stress. Experimental findings on a number of existing–emerging therapeutic agents and natural compounds against key targets are promising. The lack of large clinical trials with adequate follow-up periods is a gap that requires addressing to validate the emerging therapeutic agents. Five therapeutic components, which include agents to mitigate the AGE–RAGE axis, improved biomarkers for risk stratification, better renal dysfunction management, adjunctive anti-inflammatory–antioxidant therapies, and innovative neuromuscular stimulation for rehabilitation, are identified. A comprehensive therapeutic strategy that features all the identified components is needed for outcome improvement in diabetic stroke patients.https://www.mdpi.com/2218-273X/12/11/1712advanced glycation end products—AGEsreceptor for AGE (RAGE)high-mobility group box 1 (HMGB1) nuclear proteinLeukotriene B4pathomechanismsdiabetes mellitus |
| spellingShingle | Nivedita L. Rao Greeshma B. Kotian Jeevan K. Shetty Bhaskara P. Shelley Mackwin Kenwood Dmello Eric C. Lobo Suchetha Padar Shankar Shellette D. Almeida Saiqa R. Shah Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke Biomolecules advanced glycation end products—AGEs receptor for AGE (RAGE) high-mobility group box 1 (HMGB1) nuclear protein Leukotriene B4 pathomechanisms diabetes mellitus |
| title | Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke |
| title_full | Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke |
| title_fullStr | Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke |
| title_full_unstemmed | Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke |
| title_short | Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke |
| title_sort | receptor for advanced glycation end product organ crosstalk and pathomechanism targets for comprehensive molecular therapeutics in diabetic ischemic stroke |
| topic | advanced glycation end products—AGEs receptor for AGE (RAGE) high-mobility group box 1 (HMGB1) nuclear protein Leukotriene B4 pathomechanisms diabetes mellitus |
| url | https://www.mdpi.com/2218-273X/12/11/1712 |
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