rones and acetylcholine deficit in certain brain structures. In this connection, inhibitors of cholinesterases capa-
ble 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 cho-
linesterases, 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
-secretase of amyloid precursor protein (APP) which partici-pates 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 24hours 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
-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.