Enhancing the Therapeutic Effect in Alzheimer's Disease Drugs: The role of Polypharmacology and Cholinesterase inhibitors

Alzheimer's disease (AD) is a devastating syndrome that accounts for 60–70 % of all dementia cases, putting an enormous burden on global healthcare and economy. Unfortunately, there no cure AD, the currently approved drugs are limited in their effects. Given various pathological mechanisms behind “one-target, one-drug” paradigm drug design became obsolete, new paradigm, polypharmacology, emerged. Consequently, greater focus has been put towards multi-target directed ligands (MTDLs), as these can regulate several targets operating network. Parallel to that, cholinesterase inhibitors have regained popularity after decades being considered only symptomatic agents with disease-modifying properties. In this review, current AD hypotheses therapeutic targets, concept polypharmacology pathology importance cholinesterases pathogenesis biochemical processes discussed, final overview development cholinesterase-based MTDLs.