Article (Scientific journals)
The Parkinson's Disease-Associated LRRK2 Mutation R1441G Inhibits Neuronal Differentiation of Neural Stem Cells.
Bahnassawy, Lamia A; Nicklas, Sarah; Palm, Thomas et al.
2013In Stem Cells and Development
Peer Reviewed verified by ORBi


Full Text
Publisher postprint (347.93 kB)
Request a copy

All documents in ORBilu are protected by a user license.

Send to


Abstract :
[en] Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause familial as well as sporadic Parkinson's disease (PD) that is characterized by an age-dependent degeneration of dopaminergic neurons. LRRK2 is strongly expressed in neural stem cells (NSCs), but still the exact molecular function of LRRK2 in these cells remains unknown. By performing a systemic analysis of the gene expression profile of LRRK2-deficient NSCs, we found that the expression of several PD-associated genes, such as oxidation and reduction in mitochondria, are deregulated on LRRK2 absence. Our data, indeed, indicate that LRRK2 regulates the level of cellular oxidative stress and thereby influences the survival of NSCs. Furthermore, the lack of LRRK2 leads to an up-regulation of neuronal differentiation-inducing processes, including the Let-7a pathway. On the other hand, the constitutive mutant of LRRK2(R1441G), known to cause PD, leads to down-regulation of the same pathway. In agreement with the function of Let-7a during neuronal differentiation, LRRK2-deficient NSCs differentiate faster than wild-type cells, while LRRK2(R1441G)-expressing NSCs show impaired neuronal differentiation. These results might help better characterize the molecular mechanisms underlying the role of LRRK2 in NSCs and would further improve potential cell-replacement strategies as well as drug discovery approaches.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Developmental and Cellular Biology (Schwamborn Group)
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bahnassawy, Lamia A
Nicklas, Sarah
Palm, Thomas
Menzl, Ingeborg
Birzele, Fabian
Gillardon, Frank
Schwamborn, Jens Christian ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
Language :
Title :
The Parkinson's Disease-Associated LRRK2 Mutation R1441G Inhibits Neuronal Differentiation of Neural Stem Cells.
Publication date :
Journal title :
Stem Cells and Development
Publisher :
Mary Ann Liebert, Inc.
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 22 June 2013


Number of views
328 (34 by Unilu)
Number of downloads
13 (13 by Unilu)

Scopus citations®
Scopus citations®
without self-citations
WoS citations


Similar publications

Contact ORBilu