Computer-Aided Drug Design Approaches to Study Key Therapeutic Targets in Alzheimer’s Disease

Alzheimer’s Disease (AD) is one of the most common and complex age-related neurodegenerative disorders in elderly people. Currently there is no cure for AD, and available therapeutic alternatives only improve both cognitive and behavioral functions. For that reason, the search for anti-AD therapeutic agents with neuroprotective properties is highly demanding. Several research studies have implicated the involvement of G-Protein-Coupled Receptors (GPCRs) in diverse neurotransmitter systems that are dysregulated in AD, mainly in modulation of amyloidogenic processing of Amyloid Precursor Protein (APP) and of microtubule-associated protein tau phosphorylation and in learning and memory activities in in vivo AD models subjected to numerous behavioral procedures. In this chapter, a special focus will be given to the structure- and ligand-based in silico approaches and their applicability on the development of small molecules that target various GPCRs potentially involved in AD such as 5-hydroxytryptamine receptors, adenosine receptors, adrenergic receptors, chemokine receptors, histamine receptors, metabotropic glutamate receptors, muscarinic acetylcholine receptors, and opioid receptors.