scholarly journals Small angle X-ray scattering analysis of Cu2+-induced oligomers of the Alzheimer's amyloid β peptide

Metallomics ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 536-543 ◽  
Author(s):  
Timothy M. Ryan ◽  
Nigel Kirby ◽  
Haydyn D. T. Mertens ◽  
Blaine Roberts ◽  
Kevin J. Barnham ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition Metal ◽  
Small Angle ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

Research into causes of Alzheimer's disease and its treatment has produced a tantalising array of hypotheses about the role of transition metal dyshomeostasis, many of them on the interaction of these metals with the neurotoxic amyloid-β peptide (Aβ).

scholarly journals Identification of a novel tetrameric structure for human apolipoprotein-D

2018 ◽  
Author(s):  
Claudia S. Kielkopf ◽  
Jason K.K. Low ◽  
Yee-Foong Mok ◽  
Surabhi Bhatia ◽  
Tony Palasovski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Small Angle ◽  
The Body ◽  
Native Structure ◽  
X Ray ◽  
X Ray Scattering ◽  
Apolipoprotein D ◽  
Ray Scattering

ABSTRACTApolipoprotein-D is a 25 kDa glycosylated member of the lipocalin family that folds into an eight-stranded β-barrel with a single adjacent α-helix. Apolipoprotein-D specifically binds a range of small hydrophobic ligands such as progesterone and arachidonic acid and has an antioxidant function that is in part due to the reduction of peroxidised lipids by methionine-93. Therefore, apolipoprotein-D plays multiple roles throughout the body and is protective in Alzheimer’s disease, where apolipoprotein-D overexpression reduces the amyloid-β burden in Alzheimer’s disease mouse models.Oligomerisation is a common feature of lipocalins that can influence ligand binding. The native structure of apolipoprotein-D, however, has not been conclusively defined. Apolipoprotein-D is generally described as a monomeric protein, although it dimerises when reducing peroxidised lipids.Here, we investigated the native structure of apolipoprotein-D derived from plasma, breast cyst fluid (BCF) and cerebrospinal fluid. In plasma and cerebrospinal fluid, apolipoprotein-D was present in high-molecular weight complexes, potentially in association with lipoproteins. In contrast, apolipoprotein-D in BCF formed distinct oligomeric species. We assessed apolipoprotein-D oligomerisation using native apolipoprotein-D purified from BCF and a suite of complementary methods, including multi-angle laser light scattering, analytical ultracentrifugation and small-angle X-ray scattering. Our analyses showed that apolipoprotein-D predominantly forms a ∽95 to ∽100 kDa tetramer. Small-angle X-ray scattering analysis confirmed these findings and provided a structural model for apolipoprotein-D tetramer. These data indicate apolipoprotein-D rarely exists as a free monomer under physiological conditions and provide insights into novel native structures of apolipoprotein-D and into oligomerisation behaviour in the lipocalin family.

Alzheimer's disease imaging biomarkers using small-angle x-ray scattering

2016 ◽  
Author(s):  
Mina Choi ◽  
Nadia Alam ◽  
Eshan Dahal ◽  
Bahaa Ghammraoui ◽  
Aldo Badano
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Angle ◽  
Imaging Biomarkers ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

scholarly journals Astrocytes and neuroinflammation in Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1321-1325 ◽  
Author(s):  
Emma C. Phillips ◽  
Cara L. Croft ◽  
Ksenia Kurbatskaya ◽  
Michael J. O’Neill ◽  
Michael L. Hutton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Models Of Disease ◽  
Opposing Effects

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

scholarly journals The Role of Intersubunit Interactions for the Stabilization of the T State ofEscherichia coliAspartate Transcarbamoylase

2002 ◽  
Vol 277 (51) ◽  
pp. 49755-49760 ◽  
Author(s):  
Robin S. Chan ◽  
Jessica B. Sakash ◽  
Christine P. Macol ◽  
Jay M. West ◽  
Hiro Tsuruta ◽  
...  
Keyword(s):  
Small Angle ◽  
Structural State ◽  
Aspartate Transcarbamoylase ◽  
Wild Type ◽  
X Ray ◽  
X Ray Scattering ◽  
Intersubunit Interactions ◽  
T State ◽  
Ray Scattering

Homotropic cooperativity inEscherichia coliaspartate transcarbamoylase results from the substrate-induced transition from the T to the R state. These two alternate states are stabilized by a series of interdomain and intersubunit interactions. The salt link between Lys-143 of the regulatory chain and Asp-236 of the catalytic chain is only observed in the T state. When Asp-236 is replaced by alanine the resulting enzyme exhibits full activity, enhanced affinity for aspartate, no cooperativity, and no heterotropic interactions. These characteristics are consistent with an enzyme locked in the functional R state. Using small angle x-ray scattering, the structural consequences of the D236A mutant were characterized. The unliganded D236A holoenzyme appears to be in a new structural state that is neither T, R, nor a mixture of T and R states. The structure of the native D236A holoenzyme is similar to that previously reported for another mutant holoenzyme (E239Q) that also lacks intersubunit interactions. A hybrid version of aspartate transcarbamoylase in which one catalytic subunit was wild-type and the other had the D236A mutation was also investigated. The hybrid holoenzyme, with three of the six possible interactions involving Asp-236, exhibited homotropic cooperativity, and heterotropic interactions consistent with an enzyme with both T and R functional states. Small angle x-ray scattering analysis of the unligated hybrid indicated that the enzyme was in a new structural state more similar to the T than to the R state of the wild-type enzyme. These data suggest that three of the six intersubunit interactions involving D236A are sufficient to stabilize a T-like state of the enzyme and allow for an allosteric transition.

Identification of the role of Al-Fe-Mn-Si large casting dispersoids in age-hardenable aluminum alloys using small angle X-ray scattering

2018 ◽  
Vol 734 ◽  
pp. 51-58
Author(s):  
S. Saimoto ◽  
M.A. Singh ◽  
M.R. Langille ◽  
A. Kula ◽  
M. Niewczas
Keyword(s):  
Aluminum Alloys ◽  
Small Angle ◽  
X Ray ◽  
X Ray Scattering ◽  
Large Casting ◽  
Ray Scattering

Small-Angle X-Ray Scattering for the Discerning Macromolecular Crystallographer

2014 ◽  
Vol 67 (12) ◽  
pp. 1786 ◽  
Author(s):  
Lachlan W. Casey ◽  
Alan E. Mark ◽  
Bostjan Kobe
Keyword(s):  
Structural Biology ◽  
Small Angle ◽  
Significant Risk ◽  
Macromolecular Crystallography ◽  
Saxs Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

The role of small-angle X-ray scattering (SAXS) in structural biology is now well established, and its usefulness in combination with macromolecular crystallography is clear. However, the highly averaged SAXS data present a significant risk of over-interpretation to the unwary practitioner, and it can be challenging to frame SAXS results in a manner that maximises the reliability of the conclusions drawn. In this review, a series of recent examples are used to illustrate both the challenges for interpretation and approaches through which these can be overcome.

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