The role of acetylcholinesterase in Alzheimer’s disease: Enzymatic inhibition studies

Abstract

Alzheimer’s disease (AD) is the most common form of dementia and causes a progressive and irreversible neurodegeneration. It is related with loss of cholinergic function, which affects memory, learning and behavior [1]. Neurophathologically, AD is characterized by the presence of beta-amyloid plaques (A ) and neurofibrillary tangles (NFT) [2] and consequent degeneration of the basal forebrain cholinergic neurons [3]. The loss of cholinergic neurons leads to the progressive reduction of acetylcholine (ACh) in the brain and resulting cognitive impairment in AD [3]. As such, the enzyme acetylcholinesterase (AChE) has been one of the prime targets in search for a treatment for AD, which uses reversible inhibitors of AChE, in order to increase levels of acetylcholine (ACh) in the brain [4]. In the present study a small library of quinolinone and indole derivatives was screened for their eeAChE inhibitory activity using the Ellman method.