Peripheral and dual binding site inhibitors of acetylcholinesterase as neurodegenerative disease modifying agents

Abstract

Current treatment approaches in Alzheimer’s disease have been dominated by the use of acetylcholinesterase (AChE) inhibitors, which increase the acetylcholine concentration in the brain, thus alleviating the decline in cognitive and mental function associated with this neurodegenerative disorder. However, AChE itself has been implicated in the pathogenesis of Alzheimer’s disease and it appears that AChE may directly interact with β-amyloid, increasing the deposition of this peptide into insoluble plaques. This new role suggests that properly designed or biologically directed screened AChE inhibitors might be able to act as disease-modifying agents rather than as a mere palliative treatment. This review discloses recent discoveries of small molecules targeting the non-cholinergic actions of this well-known cholinergic enzyme.

• beta-amyloid
• acetylcholinesterase inhibitors
• Alzheimer’s disease
• protein aggregation