Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer’s Disease

Abstract: Alzheimer’s disease (AD) is a complex neurological disorder and multiple pathological factors are believed to be involved in the genesis and progression of the dis-ease. A number of hypothesis including Acetylcholinesterase, Monoamine oxidase, β-Amyloid, Tau protein etc. have been proposed for the initiation and progression of the disease. At present, acetylcholine esterase inhibitors and memantine (NMDAR antago-nist) are the only approved therapy for the symptomatic management of AD. Most of these single-target drugs have miserably failed in the treatment or halting the progression of the disease. Multi-factorial diseases like AD require complex treatment strategies that involve simultaneous modulation of a network of interacting targets. Since last few years, Multi-Target-Directed Ligands (MTDLs) strategy, drugs that can simultaneously hit mul-tiple targets, is being explored as an effective therapeutic approach for the treatment of AD. In the current review article, the authors have briefly described various pathogenic pathways associated with the AD. Importance of Multi-Target-Directed Ligands and their design strategies in recently reported articles have been discussed in detail. Potent leads identified through various structure-activity relationship studies and their drug like char-acteristics are described. Recently developed promising compounds have been summa-rized in the article. Some of these MTDLs with balanced activity profile against different targets have the potential to be developed as drug candidates for the treatment of AD.