Reference : ANALYSIS OF NEURONAL DIFFERENTIATION IN GENETIC FORMS OF PARKINSON’S DISEASE REVEALS...
Dissertations and theses : Doctoral thesis
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/33626
ANALYSIS OF NEURONAL DIFFERENTIATION IN GENETIC FORMS OF PARKINSON’S DISEASE REVEALS A NEURODEVELOPMENTAL CONTRIBUTION
English
Walter, Jonas [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
15-Sep-2017
University of Luxembourg, ​Esch-sur-Alzette, ​​Luxembourg
Doctor of Philosophy
317
[en] Parkinson’s disease ; LRRK2 ; Neurodevelopment
[en] During the mammalian embryonic neurodevelopment, all neurons descend from neuroepithelial stem cells. Accumulating evidences indicate a contribution of neurodevelopmental processes to the vulnerability to diseases. Here, we elucidate such developmental contribution in the context of Parkinson’s disease by combining high content imaging approaches, single-cell RNA sequencing, 3D image analysis, and multifactorial functional mitochondrial readouts. We found that the prominent PD-associated LRRK2-G2019S mutation accelerates dopaminergic neuron differentiation, accompanied by a reduced viability, resulting in indistinguishable dopaminergic neuron quantities. Our data indicate that the unexpected dynamics is driven by LRRK2-G2019S-dependent aberrations in gene expression as well as mitochondrial health and biogenesis of the neuroepithelial stem cell population. We conclude that LRRK2-G2019S modifies the dynamics of dopaminergic neuron fate specification during development, what may constitute a predisposition to parts of the PD-associated clinical manifestations.
http://hdl.handle.net/10993/33626
FnR ; FNR5985277 > Jonas Walter > LRRK2Mito > Analysis Of Mitophagy In Neural Stem Cells Carrying Parkinson’S Disease Associated Mutations In Lrrk2. > 01/10/2013 > 30/09/2017 > 2013

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
20171211_JonasWalter_Thesis.pdfAuthor preprint23.13 MBView/Open

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.