Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes
| Autor: | Paula P Navarro, Amanda J Lewis, Tim Moors, Jürgen Hench, Wilma D.J. van de Berg, Jing Wang, Vincenzo Bonifati, Andreas Staempfli, Markus Britschgi, Annemieke J.M. Rozemuller, Frederik Großerüschkamp, Henning Stahlberg, Stephan Frank, Evelien Huisman, Klaus Gerwert, Daniel Niedieker, Wilfred F. J. van IJcken, Yvonne de Gier, Rosmarie Sütterlin, Gabriel Schweighauser, Angela Ingrassia, Kenneth N. Goldie, Joerg Hoernschemeyer, Anne De Paepe, Sarah H Shahmoradian, Matthias E. Lauer, Johannes Erny, Alexandra Graff-Meyer, Christel Genoud, Marialuisa Quadri, Bernd Bohrmann, Daniel Castaño-Díez, Samir F. El-Mashtoly |
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| Přispěvatelé: | Clinical Genetics, Cell biology, Anatomy and neurosciences, VU University medical center, Pathology, Amsterdam Neuroscience - Neurodegeneration |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lewy Body Disease Parkinson's disease Biology Hippocampus Pathogenesis 03 medical and health sciences Membrane Lipids 0302 clinical medicine Imaging Three-Dimensional Alzheimer Disease Mesencephalon Organelle Lipidomics Exome Sequencing medicine Humans Organelles Microscopy Confocal General Neuroscience STED microscopy Parkinson Disease Human brain Intracellular Membranes Compartmentalization (fire protection) medicine.disease Substantia Nigra Microscopy Electron 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence Ultrastructure alpha-Synuclein Lewy Bodies Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Shahmoradian, S H, Lewis, A J, Genoud, C, Hench, J R, Moors, T E, Navarro, P P, Castaño-Díez, D, Schweighauser, G, Graff-Meyer, A, Goldie, K N, Sütterlin, R, Huisman, E, Ingrassia, A, Gier, Y D, Rozemuller, A J M, Wang, J, Paepe, A D, Erny, J, Staempfli, A, Hoernschemeyer, J, Großerüschkamp, F, Niedieker, D, el-Mashtoly, S F, Quadri, M, van IJcken, W F J, Bonifati, V, Gerwert, K, Bohrmann, B, Frank, S, Britschgi, M, Stahlberg, H, van de Berg, W D J & Lauer, M E 2019, ' Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes ', Nature Neuroscience, vol. 22, no. 7, pp. 1099-1109 . https://doi.org/10.1038/s41593-019-0423-2 Nature Neuroscience, 22(7), 1099-+. Nature Publishing Group Nature Neuroscience, 22(7), 1099-1109. Nature Publishing Group |
| ISSN: | 1097-6256 |
| Popis: | Parkinson's disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Key neuropathological hallmarks are Lewy bodies and Lewy neurites: neuronal inclusions immunopositive for the protein alpha-synuclein. In-depth ultrastructural analysis of Lewy pathology is crucial to understanding pathogenesis of this disease. Using correlative light and electron microscopy and tomography on postmortem human brain tissue from Parkinson's disease brain donors, we identified alpha-synuclein immunopositive Lewy pathology and show a crowded environment of membranes therein, including vesicular structures and dysmorphic organelles. Filaments interspersed between the membranes and organelles were identifiable in many but not all alpha-synuclein inclusions. Crowding of organellar components was confirmed by stimulated emission depletion (STED)-based super-resolution microscopy, and high lipid content within alpha-synuclein immunopositive inclusions was corroborated by confocal imaging, Fourier-transform coherent anti-Stokes Raman scattering infrared imaging and lipidomics. Applying such correlative high-resolution imaging and biophysical approaches, we discovered an aggregated protein-lipid compartmentalization not previously described in the Parkinsons' disease brain. |
| Databáze: | OpenAIRE |
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