Sandbox Reserved 817: Difference between revisions
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BACE1, which stand for β-site of Amyloid precursor protein Cleaving Enzyme 1, is a β secretase also known as memapsin 2. It is an aspartyl protease that initiates the formation of β-amyloid which accumulation has a huge role in the Alzeimer disease. It had been brought to light that not only BACE1 levels rise in the brain of the patients suffering from this disease but that BACE1 knock out mices can’t produce β-amyloid, effectively preventing the formation of amyloid plaques and the development of the Alzheimer disease. This discovery makes the BACE1 a very interesting drug target for Alzheimer disease.The inhibition of this enzyme is a plausible course of action and several inhibitors like the ones that will be presented are considered. However, the total inhibition of BACE1 seems to leads to physiological and behavioural troubles. That would mean that BACE1 could also be involved in several other brain functions. So the regulation of BACE1 activity by partial inhibition seems to be a prefencial method. Anyway, a good understanding of the biological function, the structure and the mechanisms of inhibition of BACE1 is highly required for drug design. | BACE1, which stand for β-site of Amyloid precursor protein Cleaving Enzyme 1, is a β secretase also known as memapsin 2. It is an aspartyl protease that initiates the formation of β-amyloid which accumulation has a huge role in the Alzeimer disease. It had been brought to light that not only BACE1 levels rise in the brain of the patients suffering from this disease but that BACE1 knock out mices can’t produce β-amyloid, effectively preventing the formation of amyloid plaques and the development of the Alzheimer disease. This discovery makes the BACE1 a very interesting drug target for Alzheimer disease.The inhibition of this enzyme is a plausible course of action and several inhibitors like the ones that will be presented are considered. However, the total inhibition of BACE1 seems to leads to physiological and behavioural troubles. That would mean that BACE1 could also be involved in several other brain functions. So the regulation of BACE1 activity by partial inhibition seems to be a prefencial method. Anyway, a good understanding of the biological function, the structure and the mechanisms of inhibition of BACE1 is highly required for drug design. | ||
== Localisation and Biological function == | == Localisation and Biological function == | ||
=== Localisation === | === Localisation === | ||
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[[Image:APP cleavage at beta and alpha site.png|right|400px|thumb|'''Figure 1 :''' Cleavage of APP by the amyloidogenic and non amyloidogenic pathways '']] | [[Image:APP cleavage at beta and alpha site.png|right|400px|thumb|'''Figure 1 :''' Cleavage of APP by the amyloidogenic and non amyloidogenic pathways '']] | ||
=== Biological functions === | === Biological functions === | ||