What is the function of the "BACE1 enzyme" in mice with amyloid plaquing of Alzheimer Disease in their brains? Does REMOVAL OF BACE1 ENZYME cause elimination of amyloid plaques already laid down in the brains of these mice?
Dennis
Dennis Mazur
BACE1 encodes the beta-secratase enzyme. In mice and people, one of the substrates for beta-secretase is the amyloid precursor protein (APP).
Beta-secretase is of interest in the context of Alzheimer's disease because it cleaves APP at a distal extracellular site, generating an intermediate, transmembrane peptide (C99 fragment) from APP. Subsequent cleavage of the C99 fragment by gamma secretase liberates the amyloid beta peptide (which is an internal sequence in the full length APP protein).
Amyloid beta accumulates in the infamous extracellular amyloid plaques characteristic of Alzheimer's disease. Therefore, BACE1 inhibition is a hot topic of research. The argument in favor of pharmacological BACE1 inhibition is that it will prevent the cleavage of APP and thereby "short circuit" the generation of amyloid beta in Alzheimer's disease.
Hence, in mice engineered to express a disease-associated variant of human APP (as well as a mutated subunit of gamma secretase), genetic deletion of BACE1 reduces amyloid beta production.
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