-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: 
-secretase • presenilin • Alzheimer's disease • amyloid 
• Notch
Abstract:
-Secretase catalyzes intramembrane proteolysis of the amyloid 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 -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 -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, -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
