Copper-Binding Amyloid Precursor Protein Undergoes a Site-Specific Fragmentation in the Reduction of Hydrogen Peroxide†

Biochemistry ◽  
1998 ◽  
Vol 37 (20) ◽  
pp. 7224-7230 ◽  
Author(s):  
Gerd Multhaup ◽  
Thomas Ruppert ◽  
Andrea Schlicksupp ◽  
Lars Hesse ◽  
Eckhard Bill ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Copper Binding ◽  
Site Specific ◽  
A Site

Identification of a novel high affinity copper binding site in the APP(145–155) fragment of amyloid precursor protein

2004 ◽  
pp. 16-22 ◽  
Author(s):  
Daniela Valensin ◽  
Francesca Maria Mancini ◽  
Marek Łuczkowski ◽  
Anna Janicka ◽  
Kornelia Wiśniewska ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Binding Site ◽  
Precursor Protein ◽  
Copper Binding ◽  
High Affinity

scholarly journals Relationship between single nucleotide polymorphisms in the 3′UTR of amyloid precursor protein and risk of Alzheimer’s disease and its mechanism

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Qiong Zhou ◽  
Lian Luo ◽  
Xiaohang Wang ◽  
Xiang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Nucleotide Polymorphisms ◽  
Amyloid Precursor Protein ◽  
Protective Factor ◽  
Precursor Protein ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
A Site

Abstract Background and objective: Deregulation of the expression of amyloid precursor protein (APP) can lead to the development of Alzheimer’s disease (AD). Recent studies have shown that many single nucleotide polymorphisms (SNPs) in the 3′ untranslated region (UTR) of APP are associated with the development of AD. Since microRNAs (miRNAs) are involved in the regulation of APP expression, we believe that the APP 3′UTR polymorphism may affect the regulation of APP expression in miRNAs. Results: The levels of miR-101-3p, miR-153-3p, miR-144-3p, miR-381-3p, and miR-383-5p in plasma of patients with AD were significantly lower than those in the control group. The APP-534G/A site A allele was a protective factor for AD risk (adjusted odds ratio (OR) = 0.700, 95% confidence interval (95% CI): 0.573–0.840, P<0.001). The APP-369C/G site variation was not associated with AD risk. The APP-118C/A site A allele was a protective factor for AD (adjusted OR = 0.762, 95% CI: 0.639–0.897, P=0.001). The APP-534G/A site mutation affects the regulation of APP protein expression by miR-101-3p, miR-144-3p, miR-153-3p, and miR-381-3p, and the mutation of the APP-118C/A site affects miR-101-3p, miR-144-3p, miR-153-3p, and miR-383-5p regulation of APP expression. Conclusion: APP 3′UTR polymorphisms can affect the regulation of APP expression by miRNAs and thus affect the occurrence of AD.

scholarly journals Amyloid Precursor Protein Dimerization and Synaptogenic Function Depend on Copper Binding to the Growth Factor-Like Domain

2014 ◽  
Vol 34 (33) ◽  
pp. 11159-11172 ◽  
Author(s):  
F. Baumkotter ◽  
N. Schmidt ◽  
C. Vargas ◽  
S. Schilling ◽  
R. Weber ◽  
...  
Keyword(s):  
Growth Factor ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Copper Binding ◽  
Protein Dimerization

scholarly journals Clioquinol Mediates Copper Uptake and Counteracts Copper Efflux Activities of the Amyloid Precursor Protein of Alzheimer's Disease

2004 ◽  
Vol 279 (50) ◽  
pp. 51958-51964 ◽  
Author(s):  
Carina Treiber ◽  
Andreas Simons ◽  
Markus Strauss ◽  
Mathias Hafner ◽  
Roberto Cappai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Yeast Culture ◽  
Copper Binding ◽  
Copper Uptake ◽  
Aβ Amyloid ◽  
Intracellular Copper

The key protein in Alzheimer's disease, the amyloid precursor protein (APP), is a ubiquitously expressed copper-binding glycoprotein that gives rise to the Aβ amyloid peptide. Whereas overexpression of APP results in significantly reduced brain copper levels in three different lines of transgenic mice, knock-out animals revealed increased copper levels. A provoked rise in peripheral levels of copper reduced concentrations of soluble amyloid peptides and resulted in fewer pathogenic Aβ plaques. Contradictory evidence has been provided by the efficacy of copper chelation treatment with the drug clioquinol. Using a yeast model system, we show that adding clioquinol to the yeast culture medium drastically increased the intracellular copper concentration but there was no significant effect observed on zinc levels. This finding suggests that clioquinol can act therapeutically by changing the distribution of copper or facilitating copper uptake rather than by decreasing copper levels. The overexpression of the human APP or APLP2 extracellular domains but not the extracellular domain of APLP1 decreased intracellular copper levels. The expression of a mutant APP deficient for copper binding increased intracellular copper levels several-fold. These data uncover a novel biological function for APP and APLP2 in copper efflux and provide a new conceptual framework for the formerly diverging theories of copper supplementation and chelation in the treatment of Alzheimer's disease.

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