Targeting Endothelin in Alzheimer’s Disease: A Promising Therapeutic Approach

Abstract

Endothelin is a chemical mediator that helps in maintaining balance within the blood-brain barrier by regulating the levels of toxicants and molecules which pass through the brain, suggesting that a rise in its production determines Alzheimer’s disease. The inequity in the amyloid β occurs due to a problem in its clearance from the brain initiating the production of reactive oxygen species and superoxide that activates a cascade wherein the release of inflammatory mediators and various enzymes like endothelin-converting enzymes take place. Furthermore, the cascade increases the levels of endothelin in the brain from endothelial cells. Endothelin levels are upregulated, which can be regulated by modulating the action of endothelin-converting enzymes and endothelin receptors. Hence, endothelin paves a pathway in the treatment of Alzheimer’s disease. In this article, we have covered various mechanisms and preclinical studies that support and direct endothelin involvement in the progression of Alzheimer’s disease by using various search tools such as PubMed, Science Direct, and Medline. Conclusive outcome data were extracted that all together defy contrivance pathways, potential drugs, endothelin receptors, and endothelin enzymes in our article giving profound importance to target endothelin for prevention and treatment of Alzheimer’s disease.

A case-control study of phosphodiesterase-5 inhibitor use and Alzheimer’s disease and related dementias among male and female patients aged 65 years and older supporting the need for a phase III clinical trial

“…This constriction is the net effect of agonism at endothelin receptor A (ET A ), which mediates constriction, and endothelin receptor B (ET B ), which mediates dilation [ 54 ]. ET-1 also mediates a pro-thrombotic state by increasing platelet aggregation, which may further exacerbate cerebral blood flow deficits [ 55 ]. ET-1 is also a pro-inflammatory cytokine, which may lead to direct neuronal damage via increased formation of reactive oxygen species [ 55 ].…”

New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease

“…Reduction in RAGE activity and upregulation of LRP1 and Pgp expression will increase Aβ clearance from the brain [ 146 ]. Endothelins (ETs, distinctive peptides of 21 amino acids) are well-known vasoconstrictive agents [ 147 ]. Endothelin is a novel target of AD drug research: ET-receptor agonists and antagonists proved to be effective for the prevention of AD in preclinical studies [ 147 ].…”

"The Drug Approaches and the Role of Healthcare Professionals in the Management of Alzheimer’s Disease"

“…Patients, for the most part, wish to keep their independence, but their families worry about their safety and well-being 41 . Moreover, in the future, drug companies and researchers in the field will have to pay special attention to nutraceuticals/ bioactive substances of plant-based origin, which have shown promising potential in the therapy of diseases in general, and neurodegenerative diseases in particular, this trend of "return to nature" being a very topical one 30,[42][43][44][45][46][47] .…”