Question

Secretase family of enzymes are central to the processing of amyloid precursor proteins (APP) associated with the development of Alzheimer's disease. They have garnered much attention over the years as a possible therapeutic target for the disease. Would targeting these enzymes for inhibition be an effective strategy for preventing the onset of Alzheimer's related amyloid plaque formation. If not, can you think of another approach that might be effective that doesn't necessarily involve targeting these enzymes?

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Answer 1

Amyloid plaques formation is the common event in Alzheimer's disease. There are number of evidences observed that an A? peptide (polypeptide) or ?- amyloid form which is an oligomer responsible for the damages caused in Alzheimer's disease. The A? plaques damages the neural cells of the brain and inactivate the required cell communications and activate the immune cells which leads to inflammation. There are 3 important proteases enzymes such as ?-secretase, ?-secretase and ?-secretase which play a key role in processing of amyloid precursor protein (APP) formation. Among which the ?-secretase enzyme and ?-secretase is the main target for Alzheimer's disease. Inhibition of these enzymes theoretically should decrease the production of A? peptide. It is also evident in human research that rational thinking and good exercise protects against dementia. Apart from which a multidrug approach therapeutic targets paves way to reduce A? production.

Targeting the enzymes is Useful:

The characterization of ?-secretase or ?-site APP cleaving enzyme (BACE1), showed that the BACE1 is the promising drug target for reducing the A? peptide levels in the Alzheimer's disease. Numerous proteins have been processed by BACE1 in addition to APP, these proteins play a major role in causing the toxicity raised due to inhibition of BACE1. Although targeting the secretase family of enzymes is an effective strategy an importance to study the proteins associated with BACE1 is mandatory to have a good treatment strategic plan for the patient which also reduces the amyloid plaque formation. More number of studies has been conducted to prove that inhibition of enzymes would help in reducing the amyloid formation such as eg: 1) invitro assays with different cell lines 2) protein analysis 3) genetic polymorphism studies of the gene encoding the enzyme

Other sources of treatment:

In recent years though the inhibition of the enzymes is the effective treatment strategy several approaches has been made without involving these enzymes such as a) drugs used to reduce / lower the cholesterol level is tested to remove the ?-amyloids. Apart from which several b) natural products eg) Genistein from Soy beans are capable of inhibiting amyloids formations have been studied and proved in animal models.