Modeling Copper Binding to the Amyloid-β Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction

2012 ◽  
Vol 116 (39) ◽  
pp. 11899-11910 ◽  
Author(s):  
Sara Furlan ◽  
Christelle Hureau ◽  
Peter Faller ◽  
Giovanni La Penna
Keyword(s):  
Molecular Mechanism ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Copper Binding

Affinity of Cu+for the Copper-Binding Domain of the Amyloid-β Peptide of Alzheimer’s Disease

2011 ◽  
Vol 50 (5) ◽  
pp. 1614-1618 ◽  
Author(s):  
Heather A. Feaga ◽  
Richard C. Maduka ◽  
Monique N. Foster ◽  
Veronika A. Szalai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Binding Domain ◽  
Amyloid Β Peptide ◽  
Copper Binding

Copper Binding Induces Polymorphism in Amyloid-β Peptide: Results of Computational Models

2018 ◽  
Vol 122 (29) ◽  
pp. 7243-7252 ◽  
Author(s):  
Dinh Quoc Huy Pham ◽  
Mai Suan Li ◽  
Giovanni La Penna
Keyword(s):  
Computational Models ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Copper Binding

Computational models explain how copper binding to amyloid-β peptide oligomers enhances oxidative pathways

2019 ◽  
Vol 21 (17) ◽  
pp. 8774-8784 ◽  
Author(s):  
Giovanni La Penna ◽  
Mai Suan Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Computational Models ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Copper Binding ◽  
Aβ Peptides ◽  
Intrinsically Disordered ◽  
Disordered Peptides

Amyloid-β (Aβ) peptides are intrinsically disordered peptides and their aggregation is the major hallmark of Alzheimer's disease (AD) development.

Molecular modeling of zinc and copper binding with Alzheimer’s amyloid β-peptide

BioMetals ◽  
2007 ◽  
Vol 21 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Daxiong Han ◽  
Haiyan Wang ◽  
Pin Yang
Keyword(s):  
Molecular Modeling ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Copper Binding

Modelling Copper Binding to the Amyloid-β Peptide in Alzheimer

2010 ◽  
Vol 63 (3) ◽  
pp. 345 ◽  
Author(s):  
V. Chandana Epa ◽  
Victor A. Streltsov ◽  
Joseph N. Varghese
Keyword(s):  
Reactive Oxygen Species ◽  
Binding Site ◽  
Reactive Oxygen Species Generation ◽  
Computational Modelling ◽  
Amyloid Β ◽  
Reactive Oxygen ◽  
Oxidative Modification ◽  
Amyloid Β Peptide ◽  
Oxygen Species ◽  
Copper Binding

Oxidative modification due to reactive oxygen species generated by Cu2+ bound to the amyloid-β peptide may be one of the sources of neurodegeneration observed in Alzheimer’s disease. Understanding the structure and function of the copper binding site can assist in the design of effective therapeutics. This paper highlights some of the most significant recent developments in computational modelling studies of the structure of the binding site and reaction mechanisms of reactive oxygen species generation.

Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein

2005 ◽  
Vol 33 (2) ◽  
pp. 335-338 ◽  
Author(s):  
N.M. Hooper
Keyword(s):  
Amyloid Precursor Protein ◽  
Lipid Rafts ◽  
Prion Protein ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Peptide ◽  
Copper Binding ◽  
Secretase Activity ◽  
Aβ Amyloid ◽  
A Disintegrin And Metalloproteinase

In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the β- and γ-secretases to release the Aβ (amyloid-β) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved by α-secretase within the Aβ domain, precluding deposition of intact Aβ peptide. The cellular form of the PrPC (prion protein) undergoes reactive oxygen species-mediated β-cleavage within the copper-binding octapeptide repeats or, alternatively, α-cleavage within the central hydrophobic neurotoxic domain. In addition, PrPC is shed from the membrane by the action of a zinc metalloprotease. Members of the ADAM (a disintegrin and metalloproteinase) family of zinc metalloproteases, notably ADAM10 and TACE (ADAM17) display α-secretase activity towards APP and appear to be responsible for the α-cleavage of PrPC. The amyloidogenic cleavage of APP by the β- and γ-secretases appears to occur preferentially in cholesterol-rich lipid rafts, while the conversion of PrPC into the infectious form PrPSc also appears to occur in these membrane domains.

A copper-binding site in the cytoplasmic domain of BACE1 identifies a possible link to metal homoeostasis and oxidative stress in Alzheimer's disease

2007 ◽  
Vol 35 (3) ◽  
pp. 571-573 ◽  
Author(s):  
C. Dingwall
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Cytoplasmic Domain ◽  
Major Constituent ◽  
Amyloid Β Peptide ◽  
Copper Binding ◽  
App Processing ◽  
Aβ Amyloid

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.

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