Fecha de publicación: 02/12/2022 Fuente: Wipo "olive oil" Target specific inhibition of BACE-1 using olive compound, Wedelosin for inhibition of Alzheimer’s DiseaseAbstract:BACE1 (ß-site amyloid precursor protein cleaving enzyme 1) was first cloned and characterized in 1999. Without it, no monomeric forms of amyloid-ß can be generated, including A42, which aggregates into bioactive conformational species and presumably causes toxicity in Alzheimer's disease (AD). The discovery that BACE1 concentrations and rates of activity are higher in AD brains and body fluids lends support to the idea that BACE1 plays a critical role in AD pathogenesis. As a result, BACE1 is a promising therapeutic target for decreasing A-ß production in the early stages of AD. Outside of the amyloidogenic pathway, BACE1 comprises substrates that may be important for synaptic plasticity and homeostasis. Early-onset familial AD (FAD) is caused by mutations in three genes (amyloid precursor protein [APP] and presenilin 1 and 2 [PS1 and PS2]). These mutations cause FAD by directly increasing production of the toxic, plaque-promoting Aß42 peptide. Amyloid plaques, composed primarily of A-ß, gradually form in the brains of A-ß patients. It is expected that therapeutic tactics that aim to lower the levels of A-ß in the brain should prove effective for the treatment of AD, given the substantial relationship that exists between A-ß and AD. Inhibiting the enzymes that are responsible for the production of A-ß could be one such technique. The big type I membrane protein APP is broken down to produce A-ß as a byproduct of this process. Endo-proteolysis of APP results in the release of the A-ß peptide, and this process is carried out by two proteases known as ß- and gamma-secretase. Recent research has led to the identification of the molecules that are responsible for these proteolytic actions. Several pieces of evidence point to the possibility that the PS1 and PS2 proteins are gamma-secretase, and it has been demonstrated that the novel transmembrane aspartic protease, ß-site APP-cleaving enzyme 1 is the identity of ß-secretase (BACE1; also called Asp2 and memapsin 2). BACE2, a protease that is homologous to BACE1, was also found, and the two enzymes together establish a new family of transmembrane aspartic proteases. BACE2 was found in the same research as BACE1. Because BACE1 possesses all of the functional characteristics of ß-secretase and because it is the primary enzyme that initiates the synthesis of A-ß, it is an interesting therapeutic target for AD. We have used Oleuropein, as standard olive oil constituent which on comparing with Wedelosin have shown a poor binding affinity of -6.8 kcal/mol. Thus, this study perhaps comprehends the efficiency of Wedelosin as lead molecule against BACE1 protein for future therapeutic purpose in AD with the efficacy of -11.8 kcal/mol.