| 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  [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 |
| File(s) associated to this reference | ||||||||||||||
|
Fulltext file(s):
| ||||||||||||||
All documents in ORBilu are protected by a user license.
