The amyloidogenic processing pathway of the APP (amyloid precursor protein) generates Aβ (amyloid β-peptide), the major constituent in Alzheimer's disease senile plaques. This processing is catalysed by two unusual membrane-localized aspartic proteinases, β-secretase [BACE1 (β-site APP-cleaving enzyme 1)] and the γ-secretase complex. There is a clear link between APP processing and copper homoeostasis in the brain. APP binds copper and zinc in the extracellular domain and Aβ also binds copper, zinc and iron. We have found that a 24-residue peptide corresponding to the C-terminal domain of BACE1 binds a single copper(I) atom with high affinity through cysteine residues. We also observed that the cytoplasmic domain of BACE1 interacts with CCS, the dedicated copper chaperone for SOD1 (superoxide dismutase 1). Overproduction of BACE1 reduces SOD1 activity in cells. Consequently, SOD1 activity, cytosolic copper and ectodomain cleavage of APP are linked through BACE1.
Skip Nav Destination
Article navigation
June 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
May 22 2007
A copper-binding site in the cytoplasmic domain of BACE1 identifies a possible link to metal homoeostasis and oxidative stress in Alzheimer's disease
C. Dingwall
1Pharmaceutical Sciences Research Division, King's College London, Franklin-Wilkins Building, Stamford Street, London SE1 9NH, U.K.
2email [email protected]
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 02 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (3): 571–573.
Article history
Received:
February 02 2007
Citation
C. Dingwall; A copper-binding site in the cytoplasmic domain of BACE1 identifies a possible link to metal homoeostasis and oxidative stress in Alzheimer's disease. Biochem Soc Trans 1 June 2007; 35 (3): 571–573. doi: https://doi.org/10.1042/BST0350571
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Get Email Alerts
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |