| Reference : Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. |
| Scientific journals : Article | |||
| Life sciences : Genetics & genetic processes | |||
| http://hdl.handle.net/10993/17143 | |||
| Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. | |
| English | |
| Strauss, Karsten M. [> >] | |
| Martins, Luisa [] | |
| Plun-Favreau, Helene [> >] | |
| Marx, Frank P. [> >] | |
| Kautzmann, Sabine [> >] | |
| Berg, Daniela [> >] | |
| Gasser, Thomas [> >] | |
| Wszolek, Zbginiew [> >] | |
| Muller, Thomas [> >] | |
| Bornemann, Antje [> >] | |
| Wolburg, Hartwig [> >] | |
| Downward, Julian [> >] | |
| Riess, Olaf [> >] | |
| Schulz, Jorg B. [> >] | |
Krüger, Rejko  [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit] | |
| 2005 | |
| Human molecular genetics | |
| 14 | |
| 15 | |
| 2099-111 | |
| Yes (verified by ORBilu) | |
| 0964-6906 | |
| England | |
| [en] Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Brain/metabolism ; Cell Death ; Cells, Cultured ; DNA Mutational Analysis ; Female ; Gene Expression Regulation ; Humans ; Male ; Membrane Potentials ; Mice ; Middle Aged ; Mitochondria/metabolism/ultrastructure ; Mitochondrial Proteins ; Models, Molecular ; Molecular Sequence Data ; Parkinson Disease/genetics/metabolism/pathology ; Point Mutation ; Sequence Homology, Amino Acid ; Serine Endopeptidases/genetics/metabolism ; Transfection | |
| [en] Recently targeted disruption of Omi/HtrA2 has been found to cause neurodegeneration and a parkinsonian phenotype in mice. Using a candidate gene approach, we performed a mutation screening of the Omi/HtrA2 gene in German Parkinson's disease (PD) patients. In four patients, we identified a novel heterozygous G399S mutation, which was absent in healthy controls. Moreover, we identified a novel A141S polymorphism that was associated with PD (P<0.05). Both mutations resulted in defective activation of the protease activity of Omi/HtrA2. Immunohistochemistry and functional analysis in stably transfected cells revealed that S399 mutant Omi/HtrA2 and to a lesser extent, the risk allele of the A141S polymorphism induced mitochondrial dysfunction associated with altered mitochondrial morphology. Cells overexpressing S399 mutant Omi/HtrA2 were more susceptible to stress-induced cell death than wild-type. On the basis of functional genomics, our results provide a novel link between mitochondrial dysfunction and neurodegeneration in PD. | |
| Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) | |
| http://hdl.handle.net/10993/17143 |
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