Membrane and surface interactions of Alzheimer's Aβ peptide--insights into the mechanism of cytotoxicity.
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TLDR
Oligomeric Aβ has been observed to bind more avidly to membranes and cause greater permeation than fibrillar Aβ, which has implications with respect to understanding the causes of Alzheimer’s disease.Abstract:
Alzheimer’s disease is the most common form of dementia and its pathological hallmarks include the loss of neurones through cell death, as well as the accumulation of amyloid fibres in the form of extracellular neuritic plaques. Amyloid fibrils are composed of the amyloid-β peptide (Aβ), which is known to assemble to form ‘toxic’ oligomers that may be central to disease pathology. Aβ is produced by cleavage from the amyloid precursor protein within the transmembrane region, and the cleaved peptide may retain some membrane affinity. It has been shown that Aβ is capable of specifically binding to phospholipid membranes with a relatively high affinity, and that modulation of the composition of the membrane can alter both membrane–amyloid interactions and toxicity. Various biomimetic membrane models have been used (e.g. lipid vesicles in solution and tethered lipid bilayers) to examine the binding and interactions between Aβ and the membrane surfaces, as well as the resulting permeation. Oligomeric Aβ has been observed to bind more avidly to membranes and cause greater permeation than fibrillar Aβ. We review some of the recent advances in studying Aβ–membrane interactions and discuss their implications with respect to understanding the causes of Alzheimer’s disease.read more
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Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies
Jessica Nasica-Labouze,Phuong H. Nguyen,Fabio Sterpone,Olivia Berthoumieu,Nicolae-Viorel Buchete,Sébastien Côté,Alfonso De Simone,Andrew J. Doig,Peter Faller,Angel E. Garcia,Alessandro Laio,Mai Suan Li,Simone Melchionna,Normand Mousseau,Yuguang Mu,Anant K. Paravastu,Samuela Pasquali,David J. Rosenman,Birgit Strodel,Bogdan Tarus,John H. Viles,Tong Zhang,Tong Zhang,Chunyu Wang,Philippe Derreumaux,Philippe Derreumaux +25 more
TL;DR: Simulations Complement Experimental Studies Jessica Nasica-Labouze, Phuong H. Nguyen, Fabio Sterpone,† Olivia Berthoumieu,‡ Nicolae-Viorel Buchete, Sebastien Cote, Alfonso De Simone, Andrew J. Doig, and Philippe Derreumaux are authors of this paper.
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Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases
TL;DR: Advances in strategies to harness the power of the natural cellular protein-folding machinery through pharmacological activation of heat shock transcription factor 1 — the master activator of chaperone protein gene expression — to treat neurodegenerative diseases are reviewed.
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Ion Channel Formation by Amyloid-β42 Oligomers but not Amyloid-β40 in Cellular Membranes
TL;DR: It is demonstrated that only Aβ(1–42) contains unique structural features that facilitate membrane insertion and channel formation, now aligning ion channel formation with the differential neurotoxic effect of Aβ (1–40) and A β(1-42) in Alzheimer's disease.
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The cell biology of prion-like spread of protein aggregates: mechanisms and implication in neurodegeneration.
TL;DR: The present review analyses and discusses the evidence supporting prion-like spreading of amyloidogenic proteins, especially focusing on the cellular and molecular mechanisms and their significance.
References
More filters
Journal ArticleDOI
Alzheimer's disease: the amyloid cascade hypothesis
John Hardy,Gerald A. Higgins +1 more
TL;DR: An extensive catalog of genes that act in a migrating cell is provided, unique molecular functions involved in nematode cell migration are identified, and similar functions in humans are suggested.
Journal ArticleDOI
The molecular pathology of Alzheimer's disease.
TL;DR: The salient features of the altered biochemistry of AD brain tissue and the possible role of these changes in the pathogenesis of this complex disease are reviewed here.
Journal ArticleDOI
Structure of the cross-beta spine of amyloid-like fibrils.
Rebecca Nelson,Michael R. Sawaya,Melinda Balbirnie,Anders Ø. Madsen,Anders Ø. Madsen,Christian Riekel,Robert Grothe,David Eisenberg +7 more
TL;DR: The atomic structure of the cross-β spine illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.
Journal ArticleDOI
3D structure of Alzheimer's amyloid-β(1–42) fibrils
Thorsten Lührs,Christiane Ritter,Marc Adrian,Dominique Riek-Loher,Bernd Bohrmann,Heinz Döbeli,David Schubert,Roland Riek +7 more
TL;DR: The 3D structure of the fibrils comprising Aβ(1–42), which was obtained by using hydrogen-bonding constraints from quenched hydrogen/deuterium-exchange NMR, side-chain packing constraints from pairwise mutagenesis studies, and parallel, in-register β-sheet arrangement from previous solid-state NMR studies, explains the sequence selectivity, the cooperativity, and the apparent unidirectionality of Aβ fibril growth.
Journal ArticleDOI
A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR
Aneta T. Petkova,Yoshitaka Ishii,John J. Balbach,Oleg N. Antzutkin,Richard D. Leapman,Frank Delaglio,Robert Tycko +6 more
TL;DR: A structural model for amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1–40) is presented, based on a set of experimental constraints from solid state NMR spectroscopy and incorporates the cross-β structural motif established by x-ray fiber diffraction.
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