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: Martin Kiechle, Patrizia Voehringer, Diana Wiesner, Birgit Liss, Rosanna Parlato, Olena Sakk, Bjoern von Einem, Veselin Grozdanov, Albert C. Ludolph, Daniel Markx, Boris Ferger, Lennart Höfs, Pamela J. McLean, Karin M Danzer, Paul Walther, Bernd Baumann, Soeren Lukassen, Jochen H. Weishaupt, Björn H. Falkenburger, Arif B. Ekici, Benjamin Mayer

المصدر: Cell Reports, Vol 29, Iss 9, Pp 2862-2874.e9 (2019)

مصطلحات موضوعية: 0301 basic medicine, Yellow fluorescent protein, Phosphorylierung, animal diseases, Protein combining, PROPAGATION, Mice, chemistry.chemical_compound, DDC 570 / Life sciences, 0302 clinical medicine, PARKINSONS-DISEASE, heterocyclic compounds, Phosphorylation, lcsh:QH301-705.5, Neurons, biology, Chemistry, Neurodegenerative diseases, Neurodegeneration, NEURODEGENERATION, Brain, Synapse, Cell biology, Parkinson disease, alpha-Synuclein, EXPRESSION, Genetically modified mouse, General Biochemistry, Genetics and Molecular Biology, Presynapse, 03 medical and health sciences, Gaussia, ddc:570, Substantia nigra, medicine, Animals, Humans, Parkinson-Krankheit, Luciferase, ddc:610, Synaptic transmission, SYNAPTIC FAILURE, Alpha-synuclein, biology.organism_classification, medicine.disease, DYSFUNCTION, nervous system diseases, Disease Models, Animal, 030104 developmental biology, lcsh:Biology (General), nervous system, health occupations, biology.protein, DDC 610 / Medicine & health, 030217 neurology & neurosurgery

الوصف: Intracellular accumulation of α-synuclein (α-syn) and formation of Lewy bodies are neuropathological characteristics of Parkinson’s disease (PD) and related α-synucleinopathies. Oligomerization and spreading of α-syn from neuron to neuron have been suggested as key events contributing to the progression of PD. To directly visualize and characterize α-syn oligomerization and spreading in vivo, we generated two independent conditional transgenic mouse models based on α-syn protein complementation assays using neuron-specifically expressed split Gaussia luciferase or split Venus yellow fluorescent protein (YFP). These transgenic mice allow direct assessment of the quantity and subcellular distribution of α-syn oligomers in vivo. Using these mouse models, we demonstrate an age-dependent accumulation of a specific subtype of α-syn oligomers. We provide in vivo evidence that, although α-syn is found throughout neurons, α-syn oligomerization takes place at the presynapse. Furthermore, our mouse models provide strong evidence for a transsynaptic cell-to-cell transfer of de novo generated α-syn oligomers in vivo.
publishedVersion

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09f7eec851a6dda0432a33e23c16134bTest
https://doi.org/10.1016/j.celrep.2019.10.089Test