References of "Berger, Klaus"
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See detailMutation analysis of the neurofilament M gene in Parkinson's disease.
Krüger, Rejko UL; Fischer, Christian; Schulte, Thorsten et al

in Neuroscience letters (2003), 351(2), 125-9

Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 ... [more ▼]

Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 familial and sporadic PD patients. Two polymorphisms (Ala475Thr and Gly697Arg) occurred at similar frequencies in PD patients and controls. A Pro725Gln substitution and a deletion of valine in position 829 were identified in two PD patients. These substitutions affect residues of the NF-M protein that are highly conserved among different species. None of our patients carried the Gly336Ser substitution, which has been described in familial PD. Our results argue against a major role of NF-M in PD. However, rare variants of the NF-M gene may act as susceptibility factors for PD and functional analyses of the identified variations are warranted to decipher possible mechanisms in neurodegeneration. [less ▲]

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See detailIdentification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease.
Marx, Frank P.; Holzmann, Carsten; Strauss, Karsten M. et al

in Human molecular genetics (2003), 12(11), 1223-31

Synphilin-1 is linked to the pathogenesis of Parkinson's disease (PD) based on its identification as an alpha-synuclein (PARK1) and parkin (PARK2) interacting protein. Moreover, synphilin-1 is a component ... [more ▼]

Synphilin-1 is linked to the pathogenesis of Parkinson's disease (PD) based on its identification as an alpha-synuclein (PARK1) and parkin (PARK2) interacting protein. Moreover, synphilin-1 is a component of Lewy bodies (LB) in brains of sporadic PD patients. Therefore, we performed a detailed mutation analysis of the synphilin-1 gene in 328 German familial and sporadic PD patients. In two apparently sporadic PD patients we deciphered a novel C to T transition in position 1861 of the coding sequence leading to an amino acid substitution from arginine to cysteine in position 621 (R621C). This mutation was absent in a total of 702 chromosomes of healthy German controls. To define a possible role of mutant synphilin-1 in the pathogenesis of PD we performed functional analyses in SH-SY5Y cells. We found synphilin-1 capable of producing cytoplasmic inclusions in transfected cells. Moreover we observed a significantly reduced number of inclusions in cells expressing C621 synphilin-1 compared with cells expressing wild-type (wt) synphilin-1, when subjected to proteasomal inhibition. C621 synphilin-1 transfected cells were more susceptible to staurosporine-induced cell death than cells expressing wt synphilin-1. Our findings argue in favour of a causative role of the R621C mutation in the synphilin-1 gene in PD and suggest that the formation of intracellular inclusions may be beneficial to cells and that a mutation in synphilin-1 that reduces this ability may sensitize neurons to cellular stress. [less ▲]

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See detail14-3-3 protein is a component of Lewy bodies in Parkinson's disease-mutation analysis and association studies of 14-3-3 eta.
Ubl, Andreas; Berg, Daniela; Holzmann, Carsten et al

in Molecular Brain Research (2002), 108(1-2), 33-9

Mutations in alpha-synuclein have been identified in some rare families with autosomal dominant Parkinson's disease (PD). The synuclein gene family shares physical and functional homology with 14-3-3 ... [more ▼]

Mutations in alpha-synuclein have been identified in some rare families with autosomal dominant Parkinson's disease (PD). The synuclein gene family shares physical and functional homology with 14-3-3 proteins and binds to 14-3-3 proteins and to its ligands. We therefore investigated whether 14-3-3 proteins are also involved in the pathogenesis of PD. Here we demonstrate that 14-3-3 proteins are colocalized with Lewy bodies in PD. We investigated the 14-3-3 eta (YWHAH) gene by mutation analysis and association studies as it maps to human chromosome 22q12.1-q13.1, a region which has been recently implicated in PD and carried out immunohistochemical studies of Lewy bodies with two different 14-3-3 eta antibodies. In 358 sporadic and familial PD patients, disease causing mutations were not identified. Furthermore, association studies with intragenic polymorphisms do not provide evidence for an involvement of 14-3-3 eta in the pathogenesis of PD. In accordance with these findings, there was no staining of substantia nigra Lewy bodies with antibodies specific for the 14-3-3 eta subunit. [less ▲]

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See detailPolymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease.
Schulte, Thorsten; Schols, Ludger; Muller, Thomas et al

in Neuroscience letters (2002), 326(1), 70-2

Several lines of evidence indicate that immune mechanisms are involved in the pathogenesis of neurodegenerative disorders. Activated immunocompetent cells and inflammatory cytokines are present in ... [more ▼]

Several lines of evidence indicate that immune mechanisms are involved in the pathogenesis of neurodegenerative disorders. Activated immunocompetent cells and inflammatory cytokines are present in affected brain regions in patients with Alzheimer's (AD) and Parkinson's disease (PD). For AD biochemical and pathological data are supported by genetic studies identifying risk alleles for polymorphisms in regulatory regions of the interleukin-1 alpha (IL-1 alpha-889) and interleukin-1 beta (IL-1 beta-511) gene, respectively. The partially overlapping pathology and inflammatory reaction pattern between AD and PD led us to investigate these polymorphisms in a large sample of 295 German PD patients and 270 healthy controls. We found T in position -511 in the IL-1 beta gene more frequent in patients compared to controls (chi(2)=4.44, P=0.034). For the IL-1 alpha-889 polymorphism no significant difference between patients and controls was observed. [less ▲]

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See detailNeurofilament L gene is not a genetic factor of sporadic and familial Parkinson's disease.
Rahner, Nils; Holzmann, Carsten; Krüger, Rejko UL et al

in Brain research (2002), 951(1), 82-6

Mutations in two genes, alpha-synuclein and parkin, have been identified as some rare causes for familial Parkinson's disease (PD). alpha-Synuclein and parkin protein have subsequently been identified in ... [more ▼]

Mutations in two genes, alpha-synuclein and parkin, have been identified as some rare causes for familial Parkinson's disease (PD). alpha-Synuclein and parkin protein have subsequently been identified in Lewy bodies (LB). To gain further insight into the pathogenesis of PD we investigated the role of neurofilament light (NF-L), another component of LB aggregation. A detailed mutation search of the NF-L gene in 328 sporadic and familial PD patients of German ancestry revealed three silent DNA changes (G163A, C224T, C487T) in three unrelated patients. Analysis of the promoter region of the NF-L gene identified a total of three base pair substitutions defining five haplotypes. Association studies based on these haplotypes revealed no significant differences between PD patients and 344 control individuals. Therefore, NF-L is unlikely to play a major role in the pathogenesis of PD. [less ▲]

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