In Vivo Protein Complementation Demonstrates Presynaptic α-Synuclein Oligomerization and Age-Dependent Accumulation of 8–16-mer Oligomer Species
| العنوان: | In Vivo Protein Complementation Demonstrates Presynaptic α-Synuclein Oligomerization and Age-Dependent Accumulation of 8–16-mer Oligomer Species |
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| 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) |
| بيانات النشر: | Elsevier BV, 2019. |
| سنة النشر: | 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 |
| تدمد: | 2211-1247 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09f7eec851a6dda0432a33e23c16134bTest https://doi.org/10.1016/j.celrep.2019.10.089Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....09f7eec851a6dda0432a33e23c16134b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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