Review of Various Approaches to Alzheimer's Disease Treatment Have Focused Solely on ß-Secretase (BACE) As A Ligand’s Target in the Last Two Decades

Abstract

AD is the most common type of dementia, characterized by advancing memory deterioration that ultimately leads to the complete loss of intellectual and mental abilities leading to loss of the ability to carry on a conversation and respond to the environment. It can seriously affect a person’s ability to carry out daily activities. The morphological and biochemical characteristics of AD are central to modern strategies for developing new medical approaches. Amyloid plaques, which are primarily made of Ab, progressively form in the brains of AD patients, and mutations in three genes (APP, PS1, and PS2) cause FAD by increasing the synthesis of the toxic Ab42 peptide. Given the strong link between Ab and AD, therapeutic strategies that lower Ab concentrations in the brain should be useful in the treatment of AD. For over the past years, the molecular identities of these proteases remained unknown. ß-secretase has been identified as the novel transmembrane aspartic protease, ß-site APP Cleaving Enzyme 1 (BACE1, also known as Asp2 and memapsin 2). BACE2, a novel protease similar to BACE1, was also discovered, and the two BACE enzymes form a new family of transmembrane aspartic proteases. BACE1 has all of the properties of a ß-secretase, and as the key enzyme that initiates the formation of Ab, it is a promising drug target for AD. This review summarizes AD treatment from a medicinal chemistry perspective, as well as the development of novel AD remedies (BACE inhibitors).