Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

References

    1. Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, et al. Nat Med. 1997;3:67–72. - PubMed
    1. Esler W P, Kimberly W T, Ostaszewski B L, Diehl T s, Moore C L, Tsai J-Y, Rahmati T, Xia W, Selkoe D J, Wolfe M S. Nat Cell Biol. 2000;2:428–434. - PubMed
    1. Kimberly W T, Xia W, Rahmati R, Wolfe M S, Selkoe D J. J Biol Chem. 2000;275:3173–3178. - PubMed
    1. Wolfe M S, Xia W, Ostaszewski B L, Diehl T S, Kimberly W T, Selkoe D J. Nature (London) 1999;398:513–517. - PubMed
    1. Wolfe M S, Xia W, Moore C L, Leatherwood D D, Ostaszewski B L, Rahmati T, Donkor I O, Selkoe D J. Biochemistry. 1999;38:4720–4727. - PubMed