Heterocyclic Scaffolds for the Treatment of Alzheimer's Disease

Background: The treatment and diagnosis of Alzheimer's Disease (AD) are two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibrillary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcholine levels, but also play an pivotal role in A beta-aggregation during the early stages of senile plaque formation. On the other hand the difficult management of AD is also related to effective diagnostic methods and efficient assays for the study of pathological features. In such complex a wide framework, heterocyclic molecules are essential backbone to build new and selective drugs as well as diagnostic probes. Methods: The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. Results: Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six-membered heterocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. Conclusion: The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyclic compounds will be consistent and hopefully determinant.