Design, Synthesis and Evaluation of Indole Derivatives as Multifunctional Agents against Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is an age related neurodegenerative disorder characterised by progressive memory loss and cognitive impairment. It is one of several neurodegenerative disorders occurring as a result of a process of programmed cell death known as apoptosis. The process is set off by various stimuli in numerous pathways that ultimately lead to apoptosis. AD stands out as one of the leading causes of death in the elderly in today's society. The cholinergic hypothesis of AD states that there is an extensive loss of cholinergic neurons in the central nervous system that contributes to cognitive impairment. Acetylcholinesterase inhibitors decrease the breakdown of the neurotransmitter acetylcholine to maintain its post synaptic levels and compensate for the loss of functional brain cells. Amyloid ? plaque formation has been shown to be extensively involved in the pathogenesis of AD. The abnormal regulation of the amyloid precursor protein gives rise to plaques that impair neuronal homeostasis and eventually lead to apoptosis. The monoamine oxidase enzymes catalyse the hydrolysis of amine neurotransmitters such as dopamine. The process produces peroxides that cause oxidative stress alongside the depletion of neurotransmitters. Inhibition of monoamine oxidase allows for accumulation of neurotransmitters and reduces the formation of oxidative free radicals to confer neuroprotection.