Discrete conformational changes as regulators of the hydrolytic properties of beta‐amyloid (1–40)

Brzyska, Maria; Trzesniewska, Katarzyna; Gers, Tomasz; Elbaum, Danek

doi:10.1111/j.1742-4658.2006.05549.x

Cited by 3 publications

(2 citation statements)

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“…BisANS binding to hydrophobic domains present in proteins, including Ab, [31] results in a fluorescence increase and a blue shift of the dye fluorescence peak. The residues 13-21 and 30-36 were suggested as potential bisANS binding regions of Ab structure.…”

Section: IImentioning

confidence: 99%

Electrochemical and Conformational Consequences of Copper (Cu^I and Cu^II) Binding to β‐Amyloid(1–40)

et al. 2009

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Copper-induced structural rearrangements of Abeta40 structure and its redox properties are described in this study. Electrochemical and fluorescent methods are used to characterise the behaviour of Abeta-Cu species. The data suggest that time-dependent folding of Abeta-Cu species may cause changes in the redox potentials.Extracellular deposits of beta-amyloid (Abeta) into senile plaques are the major features observed in brains of Alzheimer's disease (AD) patients. A high concentration of copper has been associated with insoluble amyloid plaques. It is known that Abeta(1-40) can bind copper with high affinity, but electrochemical properties of Abeta(1-40)-Cu complexes are not well-characterised. In this study we demonstrate that complexation of copper (both as Cu(I) and Cu(II)) by Abeta(1-40) reduces the metal electrochemical activity. Formation of copper-Abeta(1-40) complexes is associated with alteration of the redox potential. The data reveal significant redox activity of fresh Abeta-copper solutions. However, copper-induced structural rearrangements of the peptide, documented by CD, correspond with time-dependent changes of formal reduction potentials (E(0')) of the complex. Fluorescent and electrochemical (cyclic voltammetry and differential pulse voltammetry) techniques suggest that reduction of the redox activity by Abeta-Cu complexes could be attributed to conformational changes that diminished copper accessibility to the external environment. According to our evidence, conformational rearrangements, induced by copper binding to amyloid, elongate the time necessary to attain the same beta-sheet content as for the metal-free peptide. Although the redox activity of Abeta-Cu complexes diminishes in a time-dependent manner, they are not completely devoid of toxicity as they destabilize red blood cells osmotic fragility, even after prolonged incubation.

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Section: IImentioning

confidence: 99%

Electrochemical and Conformational Consequences of Copper (Cu^I and Cu^II) Binding to β‐Amyloid(1–40)

et al. 2009

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“…It is thought that FTIR is more sensitive to -sheet content whereas CD measurements generally tend to underestimate -sheet relative to -helix content [96]. FTIR has been used extensively to study the conformational changes of A during assembly [97][98][99][100][101].…”

Section: Fourier-transform Infrared (Ftir) Spectroscopymentioning

confidence: 99%

Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders

Rahimi

Shanmugam²,

Bitan³

2008

CAR

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Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., light-chain and senile systemic amyloidoses, and other organ-specific diseases, such as dialysis-related amyloidosis and type-2 diabetes mellitus, also are characterized by deposition of aberrantly folded, insoluble proteins. It is debated whether the hallmark pathologic lesions are causative. Substantial evidence suggests that these aggregates are the end state of aberrant protein folding whereas the actual culprits likely are transient, pre-fibrillar assemblies preceding the aggregates. In the context of neurodegenerative amyloidoses, the proteinaceous aggregates may eventuate as potentially neuroprotective sinks for the neurotoxic, oligomeric protein assemblies. The pre-fibrillar, oligomeric assemblies are believed to initiate the pathogenic mechanisms that lead to synaptic dysfunction, neuronal loss, and disease-specific regional brain atrophy. The amyloid beta-protein (Abeta), which is believed to cause Alzheimer's disease (AD), is considered an archetypal amyloidogenic protein. Intense studies have led to nominal, functional, and structural descriptions of oligomeric Abeta assemblies. However, the dynamic and metastable nature of Abeta oligomers renders their study difficult. Different results generated using different methodologies under different experimental settings further complicate this complex area of research and identification of the exact pathogenic assemblies in vivo seems daunting. Here we review structural, functional, and biological experiments used to produce and study pre-fibrillar Abeta assemblies, and highlight similar studies of proteins involved in related diseases. We discuss challenges that contemporary researchers are facing and future research prospects in this demanding yet highly important field.

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Methods for Studying and Structure–Function Relationships of Non-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders

Rahimi¹

2014

Advances in Alzheimer's Research

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Discrete conformational changes as regulators of the hydrolytic properties of beta‐amyloid (1–40)

Cited by 3 publications

References 41 publications

Electrochemical and Conformational Consequences of Copper (Cu^I and Cu^II) Binding to β‐Amyloid(1–40)

Electrochemical and Conformational Consequences of Copper (Cu^I and Cu^II) Binding to β‐Amyloid(1–40)

Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders

Methods for Studying and Structure–Function Relationships of Non-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders

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Discrete conformational changes as regulators of the hydrolytic properties of beta‐amyloid (1–40)

Cited by 3 publications

References 41 publications

Electrochemical and Conformational Consequences of Copper (CuI and CuII) Binding to β‐Amyloid(1–40)

Electrochemical and Conformational Consequences of Copper (CuI and CuII) Binding to β‐Amyloid(1–40)

Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders

Methods for Studying and Structure–Function Relationships of Non-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders

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Product

Resources

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Electrochemical and Conformational Consequences of Copper (Cu^I and Cu^II) Binding to β‐Amyloid(1–40)

Electrochemical and Conformational Consequences of Copper (Cu^I and Cu^II) Binding to β‐Amyloid(1–40)