Sci. Aging Knowl. Environ., 19 March 2003
Vol. 2003, Issue 11, p. pe7
[DOI: 10.1126/sageke.2003.11.pe7]

PERSPECTIVES

{gamma}-Secretase--Intramembrane Protease with a Complex

Michael S. Wolfe

The author is at the Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. E-mail: mwolfe{at}rics.bwh.harvard.edu.

http://sageke.sciencemag.org/cgi/content/full/sageke;2003/11/pe7

Key Words: {gamma}-secretase • presenilin • Alzheimer's disease • amyloid {beta} • Notch

Abstract: {gamma}-Secretase catalyzes intramembrane proteolysis of the amyloid {beta} protein precursor, a process closely linked to the development of Alzheimer's disease. This protease also cleaves the transmembrane domain of the Notch receptor as part of a signaling pathway that is essential for proper embryonic develoment. Recent findings suggest that {gamma}-secretase is a complex of at least four integral membrane proteins: presenilin, nicastrin, Aph-1, and Pen-2. Assembly of these four components apparently leads to autocleavage of presenilin into two subunits that together compose the intramembranous active site of {gamma}-secretase. Understanding the mechanism of this unusual enzyme is important, as it is both a key therapeutic target and a founding member of a newly discovered class of intramembrane-cleaving proteases.

Citation: M. S. Wolfe, {gamma}-Secretase--Intramembrane Protease with a Complex. Sci. SAGE KE 2003, pe7 (19 March 2003)
http://sageke.sciencemag.org/cgi/content/full/sageke;2003/11/pe7

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