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.