Reference : 3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phe...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/37469
3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing
English
Bolognin, Silvia mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Fossépré, Marie []
Qing, Xiaobing []
Jarazo, Javier mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Ščančar, Janez []
Lucumi Moreno, Edinson mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Nickels, Sarah mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Wasner, Kobi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Ouzren, Nassima mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Walter, Jonas mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Grünewald, Anne mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Salamanca, Luis []
Fleming, Ronan M. T. []
Antony, Paul mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Schwamborn, Jens Christian mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Nov-2018
Advanced Science
Wiley
Yes
2198-3844
Weinheim
Germany
[en] iPSC ; LRRK2 ; 3D cultures ; mitochondria ; Parkinson's disease ; neurons
[en] Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific neurons, derived from induced pluripotent stem cells carrying the LRRK2‐G2019S mutation, is optimized in 3D microfluidics. The automated image analysis algorithms are implemented to enable pharmacophenomics in disease‐relevant conditions. In contrast to 2D cultures, this 3D approach reveals robust endophenotypes. High‐content imaging data show decreased dopaminergic differentiation and branching complexity, altered mitochondrial morphology, and increased cell death in LRRK2‐G2019S neurons compared to isogenic lines without using stressor agents. Treatment with the LRRK2 inhibitor 2 (Inh2) rescues LRRK2‐G2019S‐dependent dopaminergic phenotypes. Strikingly, a holistic analysis of all studied features shows that the genetic background of the PD patients, and not the LRRK2‐G2019S mutation, constitutes the strongest contribution to the phenotypes. These data support the use of advanced in vitro models for future patient stratification and personalized drug development.
Researchers ; Professionals ; Students
http://hdl.handle.net/10993/37469
10.1002/advs.201800927
H2020 ; 668738 - SysMedPD - Systems Medicine of Mitochondrial Parkinson’s Disease
FnR ; FNR11250962 > Anne Gr�newald > ProtectMove > Reduced penetrance in hereditary movement disorders: Elucidating mechanisms of endogenous disease protectionP1: Markers and Mechanisms of Reduced Penetrance in LRRK2 Mutation Carriers > 01/01/2017 > 31/12/2018 > 2016

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