Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a multi-faceted pathogenesis. So far, the therapeutic paradigm “one-compound-one-target” has failed and despite enormous efforts to elucidate the pathophysiology of AD, the disease is still incurable. The multiple factors involved in AD include amyloid aggregation to form insoluble neurotoxic plaques of Aβ, hyperphosphorylation of tau protein, oxidative stress, calcium imbalance, mitochondrial dysfunction and deterioration of synaptic transmission. These factors together, accentuate changes in the CNS homeostasis, starting a complex process of interconnected physiological damage, leading to cognitive and memory impairment and neuronal death. A recent approach for the rational design of new drug candidates, also called multitarget-directed ligand (MTDL) approach, has gained increasing attention by many research groups, which have developed a variety of hybrid compounds acting simultaneously on diverse biological targets. This review aims to show some recent advances and examples of the exploitation of MTDL approach in the rational design of novel drug candidate prototypes for the treatment of AD.