Effect of Metal Chelators on γ-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate
Joint Authors
Evin, Geneviève
Culvenor, Janetta G.
Masters, Colin L.
White, Anthony R.
Ho, Michael
Hoke, David E.
Chua, Yee Jia
Li, Qiao-Xin
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-12-28
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Gamma-secretase is involved in the production of Aβ amyloid peptides.
It cleaves the transmembrane domain of the amyloid precursor protein (APP) at alternative sites to produce Aβ and the APP intracellular domain (AICD).
Metal ions play an important role in Aβ aggregation and metabolism, thus metal chelators and ligands represent potential therapeutic agents for AD treatment.
A direct effect of metal chelators on γ-secretase has not yet been investigated.
The authors used an in vitro γ-secretase assay consisting of cleavage of APP C100-3XFLAG by endogenous γ-secretase from rodent brains and human neuroblastoma SH-SY5Y, and detected AICD production by western blotting.
Adding metalloprotease inhibitors to the reaction showed that clioquinol, phosphoramidon, and zinc metalloprotease inhibitors had no significant effect on γ-secretase activity.
In contrast, phenanthroline, EDTA, and EGTA markedly decreased γ-secretase activity that could be restored by adding back calcium and magnesium ions.
Mg2+ stabilized a 1,000 kDa presenilin 1 complex through blue native gel electrophoresis and size-exclusion chromatography.
Data suggest that Ca2+ and Mg2+ stabilize γ-secretase and enhance its activity.
American Psychological Association (APA)
Ho, Michael& Hoke, David E.& Chua, Yee Jia& Li, Qiao-Xin& Culvenor, Janetta G.& Masters, Colin L.…[et al.]. 2010. Effect of Metal Chelators on γ-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate. International Journal of Alzheimer's Disease،Vol. 2011, no. 2011, pp.1-10.
https://search.emarefa.net/detail/BIM-510792
Modern Language Association (MLA)
Ho, Michael…[et al.]. Effect of Metal Chelators on γ-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate. International Journal of Alzheimer's Disease No. 2011 (2011), pp.1-10.
https://search.emarefa.net/detail/BIM-510792
American Medical Association (AMA)
Ho, Michael& Hoke, David E.& Chua, Yee Jia& Li, Qiao-Xin& Culvenor, Janetta G.& Masters, Colin L.…[et al.]. Effect of Metal Chelators on γ-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate. International Journal of Alzheimer's Disease. 2010. Vol. 2011, no. 2011, pp.1-10.
https://search.emarefa.net/detail/BIM-510792
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-510792