HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Y.-M. Search for Related Content PubMed PubMed Citation Articles by Li, Y.-M.

-Secretase: A Catalyst of Alzheimer Disease and Signal Transduction

Department of Biological Chemistry Merck Research Laboratories West Point, PA 19486

Proteolytic processing of the amyloid precursor protein (APP) is fundamental to the plaques that develop in brain tissue afflicted by Alzheimer disease (see above). The processing of APP, not only in Alzheimer disease, but also in normal physiology, is thus a major focus of research.

-Secretase is a membrane-bound protease that cleaves within the transmembrane region of the amyloid precursor protein to generate the C termini of both major peptides that constitute the amyloid plaques found in Alzheimer disease (AD). Recent biochemical studies provide compelling evidence that presenilins, membrane-spanning proteins associated with early-onset familial AD, are novel aspartyl proteased that function within a macromolecular complex to mediate -secretase activity.These new insights underscore the role of the presenilins in regulated intramembrane proteolysis and could possibly lead to the inhibition of -secretase activity as a therapy for AD.

This article has been cited by other articles:

				L. Tarassishin, Y. I. Yin, B. Bassit, and Y.-M. Li Processing of Notch and amyloid precursor protein by {gamma}-secretase is spatially distinct PNAS, December 7, 2004; 101(49): 17050 - 17055. [Abstract] [Full Text] [PDF]

				M.-T. Lai, E. Chen, M.-C. Crouthamel, J. DiMuzio-Mower, M. Xu, Q. Huang, E. Price, R. B. Register, X.-P. Shi, D. B. Donoviel, et al. Presenilin-1 and Presenilin-2 Exhibit Distinct yet Overlapping {gamma}-Secretase Activities J. Biol. Chem., June 13, 2003; 278(25): 22475 - 22481. [Abstract] [Full Text] [PDF]