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 ![]() | |
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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