edoc

Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes

Shahmoradian, Sarah H. and Lewis, Amanda J. and Genoud, Christel and Hench, Jürgen and Moors, Tim E. and Navarro, Paula P. and Castaño-Díez, Daniel and Schweighauser, Gabriel and Graff-Meyer, Alexandra and Goldie, Kenneth N. and Sütterlin, Rosmarie and Huisman, Evelien and Ingrassia, Angela and de Gier, Yvonne and Rozemuller, Annemieke J. M. and Wang, Jing and De Paepe, Anne and Erny, Johannes and Staempfli, Andreas and Hoernschemeyer, Joerg and Großerüschkamp, Frederik and Niedieker, Daniel and El-Mashtoly, Samir F. and Quadri, Marialuisa and Van IJcken, Wilfred F. J. and Bonifati, Vincenzo and Gerwert, Klaus and Bohrmann, Bernd and Frank, Stephan and Britschgi, Markus and Stahlberg, Henning and Van de Berg, Wilma D. J. and Lauer, Matthias E.. (2019) Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes. Nature Neuroscience, 22 (7). pp. 1099-1109.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/77894/

Downloads: Statistics Overview

Abstract

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 α-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 α-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 α-synuclein inclusions. Crowding of organellar components was confirmed by stimulated emission depletion (STED)-based super-resolution microscopy, and high lipid content within α-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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
05 Faculty of Science
UniBasel Contributors:Castano Diez, Daniel and Stahlberg, Henning and Goldie, Kenneth N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature America
ISSN:1097-6256
e-ISSN:1546-1726
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:01 Oct 2020 14:58
Deposited On:14 Aug 2020 12:48

Repository Staff Only: item control page