{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:35:44Z","timestamp":1790775344300,"version":"4.1.0"},"reference-count":114,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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\u2013ischemic 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\u2013kidney\u2013muscle 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\u2013emerging 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\u2013RAGE axis, improved biomarkers for risk stratification, better renal dysfunction management, adjunctive anti-inflammatory\u2013antioxidant 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.<\/jats:p>","DOI":"10.3390\/biom12111712","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:07:23Z","timestamp":1669000043000},"page":"1712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2011-2619","authenticated-orcid":false,"given":"Nivedita L.","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greeshma B.","family":"Kotian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeevan K.","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Royal College of Surgeons in Ireland Medical University of Bahrain, Muharraq 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8550-5662","authenticated-orcid":false,"given":"Bhaskara P.","family":"Shelley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackwin Kenwood","family":"Dmello","sequence":"additional","affiliation":[{"name":"Department of Public Health, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchetha Padar","family":"Shankar","sequence":"additional","affiliation":[{"name":"College of Physiotherapy, Dayananda Sagar University, Bangalore 560111, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shellette D.","family":"Almeida","sequence":"additional","affiliation":[{"name":"School of Physiotherapy, D. Y. Patil (Deemed to be University), Navi Mumbai 400706, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiqa R.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yenepoya Medical College, Yenepoya (deemed to be University), Mangalore 575018, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.diabres.2011.10.029","article-title":"IDF Diabetes Atlas: Global Estimates of the Prevalence of Diabetes for 2011 and 2030","volume":"94","author":"Whiting","year":"2011","journal-title":"Diabetes Res. Clin. 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