المؤلفون: Marcus Fändrich, Daniel Markx, Christian Mawrin, Cornelia Loos, Stephanie Claus, Christian Haupt

المصدر: Biochemical and Biophysical Research Communications. 497:857-862

مصطلحات موضوعية: 0301 basic medicine, Amyloid, Protein Folding, Protein Conformation, Biophysics, Brain tissue, Fibril, Biochemistry, Protein Aggregates, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, Prion protein, Molecular Biology, Brain Chemistry, Amyloid beta-Peptides, Chemistry, Neurodegeneration, Cell model, Aβ peptide, Brain, Cell Biology, medicine.disease, Peptide Fragments, 030104 developmental biology, Aβ amyloid, Protein folding

الوصف: Intracerebral injection of brain extracts from Alzheimer's disease (AD) patients into appropriate mouse models was previously found to drastically accelerate the deposition of Aβ amyloid in the recipient animals indicating a prion-like activity. In this study we show that this prion-like activity can be also identified by using a cell culture model of Aβ plaque formation. Analysis of biochemical fractions of AD brain extract indicate that the seeding-activity correlated with the presence of Aβ peptide and Aβ-derived aggregates. In vitro-formed fibrils were also active but their activity was low and depending on the fibril structure and conditions of fibril formation. Our data indicate a conformational basis of the observed seeding effect and suggest the utility of our cell model for further studies on the prion-like activity of AD extracts.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0056fc946adfd44f12eb41dc6950c3ccTest
https://doi.org/10.1016/j.bbrc.2018.02.137Test

المؤلفون: Megan Garvey, Senthil Kumar, Melanie Wulff, Marcus Fändrich, Jochen Balbach, Isabel Morgado, Christian Mawrin, Daniel Markx, Uwe Knüpfer, Monika Baumann, Uwe Horn

المصدر: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 23(2)

مصطلحات موضوعية: 0301 basic medicine, Pathology, medicine.medical_specialty, Amyloid, Protein Folding, Protein Conformation, Plaque, Amyloid, macromolecular substances, Buffers, Fibril, 01 natural sciences, Models, Biological, Cell Line, Phosphates, 03 medical and health sciences, Protein structure, Internal Medicine, medicine, Humans, Nuclear Magnetic Resonance, Biomolecular, Conserved Sequence, Amyloid beta-Peptides, 010405 organic chemistry, Chemistry, Neurodegeneration, P3 peptide, Deuterium Exchange Measurement, medicine.disease, In vitro, Peptide Fragments, 0104 chemical sciences, Solutions, 030104 developmental biology, Solid-state nuclear magnetic resonance, Cell culture, Biophysics, Protein folding

الوصف: Objectives: The detailed structure of brain-derived Aβ amyloid fibrils is unknown. To approach this issue, we investigate the molecular architecture of Aβ(1–40) fibrils grown in either human cerebrospinal fluid solution, in chemically simple phosphate buffer in vitro or extracted from a cell culture model of Aβ amyloid plaque formation.Methods: We have used hydrogen–deuterium exchange (HX) combined with nuclear magnetic resonance, transmission electron microscopy, seeding experiments both in vitro and in cell culture as well as several other spectroscopic measurements to compare the morphology and residue-specific conformation of these different Aβ fibrils.Results and conclusions: Our data reveal that, despite considerable variations in morphology, the spectroscopic properties and the pattern of slowly exchanging backbone amides are closely similar in the fibrils investigated. This finding implies that a fundamentally conserved molecular architecture of Aβ peptide fold is common to Aβ fibrils.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c3b20cf386845afe087fc1b1ec8a825Test
https://pubmed.ncbi.nlm.nih.gov/26972581Test