Effects of geroprotective peptides on the activity of cholinesterases and formation of the soluble form of the amyloid precursor protein in human neuroblastoma SH-SY5Y cells

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Age related decline of cognitive functions in humans is a result of degeneration of cholinergic neurones and acetylcholine deficit in certain brain structures. In this connection, inhibitors of cholinesterases capable of preventing further decline of acetylcholine levels are widely used for treatment of cognitive disorders, in particular in Alzheimer’s disease (AD). Despite a wide range of anticholinesterase drugs available to date most of them have side-effects and are not always beneficial in older patients. Moreover, there are two forms of cholinesterases, namely acetyl- and butyrylcholinesterases (AChE and BuChE) which have different levels of their expression, localisation and functions in the brain. Since with age there is a decrease of AChE activity and an increase of BuChE, the design of selective inhibitors for each enzyme is required. In the present work the effects of synthetic geroprotective peptides vilon (Lys-Glu) and epithalon (Ala-Glu-Asp-Gly) on the activity of AChE and BuChE in human neuroblasoma cells SH-SY5Y have been studied. Also we performed an analysis of the effects of these peptides on the activity of the α-secretase of amyloid precursor protein (APP) which participates in non-amyloidogenic processing of APP releasing a soluble fragment of APP, and possibly in formation of a soluble form of AChE. It was found that incubation of cells during 24 hours in the presence of 50 nM of vilon and epithalon resulted in a decrease of the activity of soluble and membrane-bound forms of AChE and BuChE on average by 30–60%. Both peptides mostly inhibited membrane-bound forms of the enzymes but to a greater extent BuChE. Epithalon was also found to be capable of activation of α-secretase by 20–25%. The data obtained suggest that vilon and epithalon have selective anticholinesterase properties and that epithalon can also stimulate APP cleavage and increase production of its soluble neuroprotective form.