Elusive Gamma-Secretase Identified

Model of an inhibitor targeted to g-secretase interacting with presenilin. The background shows an Alzheimer's brain that carried a presenilin mutation, with immunohistochemistry revealing abundant amyloid plaques (red-orange patches). For years researchers have been perplexed by the identity of g-secretase, an enzyme that cuts amyloid precursor protein (APP) into amyloid ß (Aß) fragments that form telltale plaques in the brains of Alzheimer's patients. Now researchers from Merck Rese

Written byNadia Halim

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For years researchers have been perplexed by the identity of g-secretase, an enzyme that cuts amyloid precursor protein (APP) into amyloid ß (Aß) fragments that form telltale plaques in the brains of Alzheimer's patients. Now researchers from Merck Research Laboratories and Harvard Medical School have independently solved the mystery, bringing the field one step closer to a therapeutic approach against Alzheimer's disease (AD). "All of the new and exciting information coming out is in agreement. It looks like presenilin is the long-sought g-secretase," says Dennis Selkoe, professor of neurology at Harvard Medical School.

Presenilin 1 (PS1) has been linked to AD since PS1 was first identified and cloned in 1995.1 PS1 mutations cause a rare form of early-onset familial AD. Bart ...

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