Reference : Embryonic development of selectively vulnerable neurons in Parkinson’s disease
Scientific journals : Article
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Genetics & genetic processes
Systems Biomedicine
Embryonic development of selectively vulnerable neurons in Parkinson’s disease
Oliveira, Miguel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Balling, Rudi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Smidt, Marten mailto [University of Amsterdam > Swammerdam Institute for Life Sciences, Department of Molecular Neuroscience, Center for Neuroscience]
Fleming, Ronan MT mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
NPJ Parkinson's Disease
[en] Parkinson's disease ; Selective vulnerability ; Neurodegeneration ; Neuronal lineages ; Neurodevelopment ; Substantia nigra pars compacta ; Dopaminergic neurons ; Noradrenergic neurons ; Serotonergic neurons ; Cholinergic neurons
[en] A specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson’s disease. We synthesised the literature on transcription factors that are required to be active, or required to be inactive, in the development of each of these five brainstem regions, and at least two differentially vulnerable nuclei within each region. Certain transcription factors, e.g., Ascl1 and Lmx1b, seem to be required for specification of many brainstem regions that are susceptible to degeneration in early Parkinson’s disease. Some transcription factors can even distinguish between differentially vulnerable nuclei within the same brain region, e.g., Pitx3 is required for specification of the substantia nigra pars compacta, but not the ventral tegmental area. We do not suggest that Parkinson’s disease is a developmental disorder. In contrast, we consider identification of shared developmental trajectories as part of a broader effort to identify the molecular mechanisms that underlie the phenotypic features that are shared by selectively vulnerable neurons. Systematic in vivo assessment of fate determining transcription factors should be completed for all neuronal populations vulnerable to degeneration in early Parkinson’s disease.
Luxembourg Centre for Systems Biomedicine (LCSB): Systems Biochemistry (Fleming Group)
R-AGR-0409 > DopaMet > 01/07/2014 - 30/06/2017 > FLEMING Ronan MT
Researchers ; Students
H2020 ; 668738 - SysMedPD - Systems Medicine of Mitochondrial Parkinson’s Disease
FnR ; FNR6669348 > Miguel Oliveira > DopaMet > Reconstruction And Computational Modelling Of Dopaminergic Neuronal Metabolism > 15/09/2013 > 14/09/2017 > 2013

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