Medicinal Chemistry of Hybrids for Neurodegenerative Diseases

Introduced more than 50 years ago, molecular hybridization remains one of the most rewarding approaches when searching for new molecules against neurodegeneration. This is because hybrids ligands, which finely integrate two pharmacophoric functionalities, are inherently more adequate to face the complex and multifactorial nature of such maladies. Indeed, both Alzheimer's disease and prion diseases are multifactorial neurodegenerative disorders with several target proteins contributing to their etiology. In this chapter we discuss selected examples of hybrid compounds rationally designed to hit more than one target involved in the neurotoxic cascade, which may hold great promise for the development of new and effective drugs. There are several medicinal chemistry challenges to overcome, but the potential benefits are worth the efforts.