Critical evaluation of current Alzheimer’s drug discovery (2018–19) & futuristic Alzheimer drug model approach

[Display omitted] Alzheimer′s disease (AD), a neurodegenerative disease responsible for death of millions of people worldwide is a progressive clinical disorder which causes neurons to degenerate and ultimately die. It is one of the common causes of dementia wherein a person′s incapability to independently think, behave and decline in social skills can be quoted as major symptoms. However the early signs include the simple non-clinical symptoms such as forgetting recent events and conversations. Onset of these symptoms leads to worsened conditions wherein the AD patient suffers severe memory impairment and eventually becomes unable to work out everyday tasks. Even though there is no complete cure for AD, rigorous research has been going on to reduce the progress of AD. Currently, a very few clinical drugs are prevailing for AD treatment. So this is the need of hour to design, develop and discovery of novel anti-AD drugs. The main factors for the cause of AD according to scientific research reveals structural changes in brain proteins such as beta amyloid, tau proteins into plaques and tangles respectively. The abnormal proteins distort the neurons. Despite the high potencies of the synthesized molecules; they could not get on the clinical tests up to human usage. In this review article, the recent research carried out with respect to inhibition of AChE, BuChE, NO, BACE1, MAOs, Aβ, H3R, DAPK, CSF1R, 5-HT4R, PDE, σ1R and GSK-3β is compiled and organized. The summary is focused mainly on cholinesterases, Aβ, BACE1 and MAOs classes of potential inhibitors. The review also covers structure activity relationship of most potent compounds of each class of inhibitors alongside redesign and remodeling of the most significant inhibitors in order to expect cutting edge inhibitory properties towards AD. Alongside the molecular docking studies of the some final compounds are discussed.