Role of Endothelin-1 in Memory Loss

摘要

Endothelin (ET-1) is a 21 amino acid peptide produced by vascular endothelium from 39 amino acid precursor, big ET-1, through the actions of endothelin converting enzyme(ECE) present on the endothelial cell membrane.It is known that cerebral blood flow (CBF) as well as vascular functions are reduced in patients with Alzheimer's disease (AD) and this reduction occurs prior to the onset of dementia. The brain damage and memory disruptions that occur in AD are considered as a result of accumulation of a substance known as amyloid beta (Aβ) in the brain. Aβ increases the production of endothelin-1 (ET-1), by acting on endothelin converting enzyme-2 (ECE-2), which cleaves big endothelin resulting in the formation of ET-1 and Aβ-40. The triggered production of ET-1 in the lining of blood vessels of the brain causes them to constrict, narrowing their lumen,which reduces blood flow through the brain in patients with AD, and thereby deteriorate the oxygen and nutrients supply to nerve cells and slowdown the pace of removal of waste products, resulting to cause adverse effects on nerve cell function. The reduction in blood supply may increase the production of Aβ and thereby accelerate the progression of the AD. ET-1reduction in blood flow is achieved by targeting on specific endothelin receptors (ET A ) in the vessel walls. The down regulation of ET A receptor could be a possibility in maintaining CBF in AD and also emphasizing use of endothelin converting enzyme (ECE) as a novel Aβ degrading enzyme can reduce memory loss to an extent.