Dual inhibitors of monoamine oxidase and cholinesterase for the treatment of Alzheimer disease.

摘要

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the most prevalent cause of dementia with ageing. The etiology of this illness is rather complex and not completely known but deposits of aberrant β- amyloid protein, as well as τ-protein hyperphosphorylation, oxidative stress, dyshomeostasis of biometals and low levels of acetylcholine (ACh) seem to play a significant role. Such complex etiology of AD has encouraged active research in the development of multi-target drugs with two or more complementary biological activities, since they may represent an important advance in the treatment of this disease. Dual inhibitors combining anti-acetyl cholinesterase (AChE) and antimonoamine oxidase (MAO) activities in one molecular entity have been recently reported. Inhibition of AChE increases neurotransmission at cholinergic synapses and reduce temporally the cognitive deficit. AChE also participates in other functions related to neuronal development, differentiation, adhesion and β-amyloid protein processing. In addition MAOB inhibition retards further deterioration of cognitive functions. In this review relevant aspects about structure, mechanism and pharmacological effects of these dual inhibitors are reported.