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Review
. 2001 Sep 25;98(20):11039-41.
doi: 10.1073/pnas.211352598.

Presenilin, Notch, and the genesis and treatment of Alzheimer's disease

D J Selkoe  1
Affiliations
Review

Presenilin, Notch, and the genesis and treatment of Alzheimer's disease

D J Selkoe. Proc Natl Acad Sci U S A. .

Abstract

Elucidation of the proteolytic processing of the amyloid beta-protein precursor (APP) has revealed that one of the two proteases (gamma-secretase) that cleave APP to release amyloid beta-protein (Abeta) is likely to be presenilin. Presenilin also mediates the gamma-secretase-like cleavage of Notch receptors to enable signaling by their cytoplasmic domains. Therefore, APP and Notch may be the first identified substrates of a unique intramembranous aspartyl protease that has presenilin as its active-site component. In view of the evidence for a central role of cerebral build-up of Abeta in the pathogenesis of Alzheimer's disease, this disorder appears to have arisen in the human population as a late-life consequence of the conservation of a critical developmental pathway.

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