biomolecules-12-01712-v2.pdf (818.82 kB)
Download fileReceptor for advanced glycation end product, organ crosstalk, and pathomechanism targets for comprehensive molecular therapeutics in diabetic ischemic stroke
journal contribution
posted on 2022-11-23, 17:34 authored by Nivedita L Rao, Greeshma B Kotian, Jeevan ShettyJeevan Shetty, Bhaskara P Shelley, Mackwin Kenwood Dmello, Eric C Lobo, Suchetha Padar Shankar, Shellette D Almeida, Saiqa R ShahDiabetes 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, nitricoxide, and polyamine mechanisms are important therapeutic targets, inflicting common consequences of neuroinflammation andoxidative stress. Experimental findings on a numberof existing–emerging therapeutic agents and natural compounds against key targets are promising. The lackof 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.
History
Comments
The original article is available at https://www.mdpi.com/Published Citation
Rao NL. et al. Receptor for advanced glycation end product, organ crosstalk, and pathomechanism targets for comprehensive molecular therapeutics in diabetic ischemic stroke. Biomolecules. 2022;12:1712Publication Date
18 November 2022External DOI
Department/Unit
- RCSI Bahrain
Publisher
MDPI AGVersion
- Published Version (Version of Record)
Usage metrics
Categories
Keywords
advanced glycation end products—AGEsreceptor for AGE (RAGE)high-mobility group box 1 (HMGB1) nuclear proteinLeukotriene B4pathomechanismsdiabetes mellitusischemic strokecerebrovascular diseasetherapeutic agentscomprehensive strategiesDiabetic Ischemic StrokeMolecular TherapeuticsPathomechanism TargetsOrgan CrosstalkGlycationCentral Nervous SystemCardiology (incl. Cardiovascular Diseases)Molecular TargetsNeurology and Neuromuscular Diseases