Reference : Gene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Human health sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/48941
Gene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching and function
English
Barbuti, Peter A []
Ohnmacht, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Santos, Bruno FR []
Antony, Paul [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Massart, François [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Cruciani, Gérald [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Dording, Claire M []
Pavelka, Lukas [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
Casadei, Nicolas [University of Tübingen, Tübingen, Germany > Institute of Medical Genetics and Applied Genomics]
Kwon, Yong-Jun [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Krüger, Rejko [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
9-Nov-2021
Scientific Reports
Nature Publishing Group
11
21946
Yes (verified by ORBilu)
2045-2322
London
United Kingdom
[en] Parkinson disease ; Synuclein ; A30P ; neuron ; iPSC
[en] Parkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the alpha-synuclein protein causing an autosomal-dominant form of PD. There are limited studies assessing pathogenic SNCA mutations in patient-derived isogenic cell models. Here we provide a functional assessment of dopaminergic neurons derived from a patient harbouring the p.A30P SNCA mutation. Using two clonal gene-corrected isogenic cell lines we identified image-based phenotypes showing impaired neuritic processes. The pathological neurons displayed impaired neuronal activity, reduced mitochondrial respiration, an energy deficit, vulnerability to rotenone, and transcriptional alterations in lipid metabolism. Our data describes for the first time the mutation-only effect of the p.A30P SNCA mutation on neuronal function, supporting the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease-modifying compound screenings and drug discovery strategies.
Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
PEARL programme (FNR/P13/6682797) ; INTER programme (INTER/LEIR/18/12719318) ; NGS Competence Center Tübingen Germany (INST 37/1049-1) ; National Centre for Excellence in Research on Parkinson's disease (NCER-PD)
Researchers ; Professionals
http://hdl.handle.net/10993/48941
10.1038/s41598-021-01505-x
https://www.nature.com/articles/s41598-021-01505-x
H2020 ; 692320 - CENTRE-PD - TWINNING for a Comprehensive Clinical Centre for the Diagnosis and Treatment of Parkinson's Disease
FnR ; FNR6682797 > Rejko Krüger > Endophenotypes in Neurodegeneration > Comprehensive Assessment Of Endophenotypes In Neurodegenerative Diseases - Translating Impaired Molecular Signalling Pathways Into Novel Therapeutic Strategies For Parkinson’S Disease > 01/06/2014 > 31/05/2019 > 2013

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