The Search for Secretases

Alzheimer's disease (AD) researchers at Amgen Inc. of Thousand Oaks, Calif., appear to be the first winners in the race to find secretases, enzymes believed critical to AD onset and, potentially, to AD treatment. Considered the most promising potential drug targets for the disease, two secretases, dubbed gamma and ß, have pivotal roles in generating the neuron-suffocating plaques in the brains of AD sufferers. They work by cleaving amyloid precursor proteins (APPs) to produce amyloid &szli

Eugene Russo
Nov 7, 1999

Alzheimer's disease (AD) researchers at Amgen Inc. of Thousand Oaks, Calif., appear to be the first winners in the race to find secretases, enzymes believed critical to AD onset and, potentially, to AD treatment. Considered the most promising potential drug targets for the disease, two secretases, dubbed gamma and ß, have pivotal roles in generating the neuron-suffocating plaques in the brains of AD sufferers. They work by cleaving amyloid precursor proteins (APPs) to produce amyloid ß(Aß), the peptides that accumulate to form plaques. A third enzyme, alpha-secretase, actually cuts through the middle of Aß, preventing amyloid peptide formation--thus making its inhibition an unattractive drug target.

Since around 1990, researchers have had a pretty good idea of where these enzymes reside, what they look like, and how they operate, but they couldn't actually identify and isolate them. The race to do so began a couple of years later with the advent...

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