Distinct presenilin-dependent and presenilin-independent γ-secretases are responsible for total cellular Aβ production
✍ Scribed by Christina A. Wilson; Robert W. Doms; Virginia M.-Y. Lee
- Book ID
- 102384158
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 178 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
γ‐Secretase is the second of two proteolytic enzymes involved in the liberation of the β‐amyloid peptide (Aβ) from the amyloid precursor protein (APP). γ‐Secretase cleavage occurs at several intracellular sites, including the Golgi network and the endoplasmic reticulum/intermediate compartment (ER/IC) to produce multiple forms of the Aβ peptide that can be either secreted from the cell or remain intracellular. To date, most evidence has suggested that members of the presenilin protein family are required for γ‐secretase activity. Although it seems that presenilins are indeed necessary for the production of most secreted and intracellular Aβ particularly that generated in downstream organelles, it was shown recently that a presenilin‐independent γ‐secretase is active in the ER/IC and is responsible for the production of a portion of intracellular Aβ42. We discuss the implications of this finding for the understanding of presenilin biology and speculate on the putative identity of the presenilin‐independent cleavage activity. © 2003 Wiley‐Liss, Inc.