Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer's Disease

Abstract

The lack of an adequate therapy for Alzheimer's Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm "Multi-Target-Directed Ligands" (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.

Keywords: Alzheimer's Disease; Hybrid Molecules; Multi-Target-Directed Ligands; New Molecules Design; Review..

Fig. (1)

Some of the main current targets in AD research.

Fig. (2)

The binding pattern of dronabinol (∆9-THC; (tetrahydrocannabinol) (white) and donepezil (black) to acetylcholinesterase is shown. The represented amino acids showed in the binding site are part of PAS, CAS and the active catalytic site of the enzyme.

Fig. (3)

Conceptual map showing main trends in constructing hybrid molecules from approved molecules and well known pharmacophores, to obtain new multi-target-directed ligands.