Aβ under stress: the effects of acidosis, Cu2+-binding, and oxidation on amyloid β-peptide dimers

2018 ◽  
Vol 54 (56) ◽  
pp. 7766-7769 ◽  
Author(s):  
Qinghua Liao ◽  
Michael C. Owen ◽  
Sofia Bali ◽  
Bogdan Barz ◽  
Birgit Strodel
Keyword(s):  
Conformational Dynamics ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Acidic Environment ◽  
High Affinity

In light of the high affinity of Cu2+ for Alzheimer's Aβ1–42 and its ability to subsequently catalyze the formation of radicals, we examine the effects of Cu2+ binding, Aβ oxidation, and an acidic environment on the conformational dynamics of the smallest Aβ1–42 oligomer, the Aβ1–42 dimer.

scholarly journals High affinity binding of amyloid β -peptide to calmodulin: Structural and functional implications

2017 ◽  
Vol 486 (4) ◽  
pp. 992-997 ◽  
Author(s):  
Isaac Corbacho ◽  
María Berrocal ◽  
Katalin Török ◽  
Ana M. Mata ◽  
Carlos Gutierrez-Merino
Keyword(s):  
Amyloid Β ◽  
Affinity Binding ◽  
Amyloid Β Peptide ◽  
High Affinity Binding ◽  
High Affinity ◽  
Functional Implications

Structure- and sequence-based design of synthetic single-domain antibody libraries

2020 ◽  
Vol 33 ◽  
Author(s):  
Alexander M Sevy ◽  
Ming-Tang Chen ◽  
Michelle Castor ◽  
Tyler Sylvia ◽  
Harini Krishnamurthy ◽  
...  
Keyword(s):  
In Vitro Selection ◽  
Amyloid Β ◽  
Single Domain ◽  
Amyloid Β Peptide ◽  
Sequencing Analysis ◽  
Single Domain Antibody ◽  
High Affinity ◽  
Domain Antibody ◽  
Combine Structure

Abstract Single-domain antibody fragments known as VHH have emerged in the pharmaceutical industry as useful biotherapeutics. These molecules, which are naturally produced by camelids, share the characteristics of high affinity and specificity with traditional human immunoglobulins, while consisting of only a single heavy chain. Currently, the most common method for generating VHH is via animal immunization, which can be costly and time-consuming. Here we describe the development of a synthetic VHH library for in vitro selection of single domain binders. We combine structure-based design and next-generation sequencing analysis to build a library with characteristics that closely mimic the natural repertoire. To validate the performance of our synthetic library, we isolated VHH against three model antigens (soluble mouse PD-1 ectodomain, amyloid-β peptide, and MrgX1 GPCR) of different sizes and characteristics. We were able to isolate diverse binders targeting different epitopes with high affinity (as high as 5 nM) against all three targets. We then show that anti-mPD-1 binders have functional activity in a receptor blocking assay.

scholarly journals The Structure of the Amyloid-β Peptide High-Affinity Copper II Binding Site in Alzheimer Disease

2008 ◽  
Vol 95 (7) ◽  
pp. 3447-3456 ◽  
Author(s):  
Victor A. Streltsov ◽  
Stephen J. Titmuss ◽  
V. Chandana Epa ◽  
Kevin J. Barnham ◽  
Colin L. Masters ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Binding Site ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
High Affinity

Amyloid β-Peptide Inhibits High-Affinity Choline Uptake and Acetylcholine Release in Rat Hippocampal Slices

2002 ◽  
Vol 70 (5) ◽  
pp. 2179-2187 ◽  
Author(s):  
S. Kar ◽  
A. M. Issa ◽  
D. Seto ◽  
D. S. Auld ◽  
B. Collier ◽  
...  
Keyword(s):  
Acetylcholine Release ◽  
Hippocampal Slices ◽  
Amyloid Β ◽  
Choline Uptake ◽  
Amyloid Β Peptide ◽  
High Affinity

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Insights into amyloid disease from fly models

2014 ◽  
Vol 56 ◽  
pp. 69-83 ◽  
Author(s):  
Ko-Fan Chen ◽  
Damian C. Crowther
Keyword(s):  
Drosophila Melanogaster ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Pathogenesis ◽  
Amyloid Aggregates ◽  
Aβ Amyloid ◽  
Polypeptide Chains ◽  
Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

Analytical methods to explore Amyloid-β-Peptide variants beyond Aβ1-40 and Aβ1-42

2015 ◽  
Vol 48 (06) ◽  
Author(s):  
H Esselmann ◽  
C Hafermann ◽  
O Jahn ◽  
I Kraus ◽  
J Vogelgsang ◽  
...  
Keyword(s):  
Analytical Methods ◽  
Amyloid Β ◽  
Amyloid Β Peptide
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