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See detailTragbare und aktiv vom Parkinson-Patienten genutzte Technologie im hauslichen Umfeld: Was bringt die Zukunft?
Maetzler, W.; Krüger, Rejko UL; Muller, T. et al

in Fortschritte der Neurologie-Psychiatrie (2016), 84 Suppl 1

Parkinson’s disease (PD) is a multisystem disorder with a plethora of symptoms affecting quality of life in the home environment. Due to the rapid development of wearable technique in the health and ... [more ▼]

Parkinson’s disease (PD) is a multisystem disorder with a plethora of symptoms affecting quality of life in the home environment. Due to the rapid development of wearable technique in the health and fitness sector, an increasing number of such wearables are available to complement diagnostic strategies of PD symptoms not only in the clinical but also in the domestic environment. This development has clear advantages over clinical evaluation, as the latter is relatively subjective, time-consuming and costly, and provides only a snapshot of the condition. First results about the use of such technology for the assessment of PD symptoms (including bradykinesia, dyskinesia, tremor, daily activity and sleep behavior) in the domestic environment are promising. They suggest that these techniques can provide complementary information about the symptoms of PD patients, and have the potential to be included in future diagnostic workup concepts of routine care in PD. The use of such technique provides also the chance to more actively include patients into medical decision making processes. [less ▲]

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See detailAntiapoptotic effects of budipine.
Muller, T.; Przuntek, H.; Krüger, Rejko UL et al

in Journal of neural transmission (Vienna, Austria : 1996) (2004), 111(10-11), 1365-73

Apoptosis is one essential step for neuronal death in the nigrostriatal region in patients with Parkinson's disease. Cytotoxic tumor necrosis factor-alpha (TNF-alpha) and the proinflammatory cytokine ... [more ▼]

Apoptosis is one essential step for neuronal death in the nigrostriatal region in patients with Parkinson's disease. Cytotoxic tumor necrosis factor-alpha (TNF-alpha) and the proinflammatory cytokine interleukin-6 (Il-6) provide a proapoptotic environment. We investigated the influence of the antiparkinsonian compound budipine on the release of TNF-alpha and Il-6 in peripheral blood mononuclear cells (PBMC) and on the degree of cisplatin induced apoptotic cell death in SH-SY 5Y human neuroblastoma cells. 10(-7), 10(-8), 10(-9) mol/l of budipine significantly reduced release of TNF-alpha and Il-6 in PBMC and decreased apoptotic cell death after 50 hours and 74 hours in the SH-SY 5Y cells. Our results suggest, that budipine administration provides an antiapoptotic environment and slows neuronal apoptotic and inflammatory mediated loss of neurons. [less ▲]

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See detailExtended mutation analysis and association studies of Nurr1 (NR4A2) in Parkinson disease.
Hering, R.; Petrovic, S.; Mietz, E.-M. et al

in Neurology (2004), 62(7), 1231-2

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See detailModulation of disease risk according to a cathepsin D / apolipoprotein E genotype in Parkinson's disease.
Schulte, T.; Bohringer, S.; Schols, L. et al

in Journal of neural transmission (Vienna, Austria : 1996) (2003), 110(7), 749-55

Aspartyl protease Cathepsin D (CTSD) has been suggested to play a role in the pathogenesis of sporadic Alzheimer's disease (AD) due to interference with protein degradation mechanisms. A C224T (A38V ... [more ▼]

Aspartyl protease Cathepsin D (CTSD) has been suggested to play a role in the pathogenesis of sporadic Alzheimer's disease (AD) due to interference with protein degradation mechanisms. A C224T (A38V) polymorphism in exon 2 of the CTSD gene is reported to be associated with an increased risk for AD. The partially overlapping pathology between AD and Parkinson's disease (PD) led us to investigate the role of this polymorphism in PD. Using association studies in 457 German PD patients and 340 controls we found no evidence for direct association between the CTSD genotype and PD. However, stratification for the apolipoprotein E (APOE) epsilon4 allele suggests a protective effect of the CTSD T-allele in PD (OR = 0.24, p = 0.002). Our findings suggest interference of CTSD and APOE polymorphisms in the pathogenesis of PD, in the sense of modulating disease risk. [less ▲]

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See detailFamilial parkinsonism with synuclein pathology: clinical and PET studies of A30P mutation carriers.
Krüger, Rejko UL; Kuhn, W.; Leenders, K. L. et al

in Neurology (2001), 56(10), 1355-62

BACKGROUND: The authors identified the second known mutation in the alpha-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one ... [more ▼]

BACKGROUND: The authors identified the second known mutation in the alpha-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one German family with autosomal dominantly inherited parkinsonism (ADP). The authors studied carriers of the A30P mutation to compare the phenotype of this mutation with idiopathic PD (IPD) and to assess nigrostriatal dopaminergic function in symptomatic and preclinical mutation carriers. METHODS: The pedigree of the A30P family spans five generations with five affected individuals. The authors performed detailed neurologic examinations followed by mutation analysis in 11 living individuals. In three mutation carriers, two individuals with definite PD and one person at risk for PD, they used L-[18]F-fluoro-3,4-dihydroxyphenylalanine (F-DOPA), [11]C-raclopride (RAC), and [18]F-fluorodeoxyglucose (FDG) PET to investigate presynaptic dopaminergic function, dopamine D2 receptors, and cerebral energy metabolism. The authors studied the cognitive functions of carriers of the A30P mutation using neuropsychological screening. RESULTS: PET studies revealed striatal presynaptic dopaminergic alterations consistent with sporadic IPD in two affected family members and no evidence for nigrostriatal dopaminergic dysfunction in one presymptomatic mutation carrier. Neuropsychological testing in four mutation carriers provided evidence for cognitive impairment as a frequent and early symptom of the A30P mutation; this is also supported by regional cerebral energy metabolism alterations in the clinically presymptomatic subject. CONCLUSIONS: The phenotype of the A30P mutation in the SNCA gene is similar to that of sporadic IPD, including a high variability of the age at disease onset, ranging from 54 to 76 years. The follow-up of presymptomatic carriers of the A30P mutation may give insight into preclinical disease stages and early manifestations of PD. [less ▲]

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See detailEvaluation of the gamma-synuclein gene in German Parkinson's disease patients.
Krüger, Rejko UL; Schols, L.; Muller, T. et al

in Neuroscience letters (2001), 310(2-3), 191-3

Mutations in the alpha-synuclein gene are responsible for an autosomal-dominantly inherited form of Parkinson's disease (PD) and alpha-synuclein was found to be the major component of Lewy bodies in PD ... [more ▼]

Mutations in the alpha-synuclein gene are responsible for an autosomal-dominantly inherited form of Parkinson's disease (PD) and alpha-synuclein was found to be the major component of Lewy bodies in PD. Because of the high homology to alpha-synuclein and the abundance in neuronal tissues, we investigated the gamma-synuclein gene in PD. We analyzed 262 German PD patients and 179 healthy German controls via two polymorphisms in the gamma-synuclein gene. No significant differences in the allelic or genotypic distributions of the investigated polymorphisms were observed between patients and controls. In addition no evidence for an increased risk of combined genotypes of polymorphisms in the gamma-synuclein and the alpha-synuclein gene was found. Therefore, our results do not support a major role of the gamma-synuclein gene in PD. [less ▲]

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See detailInvolvement of alpha-synuclein in Parkinson's disease and other neurodegenerative disorders.
Krüger, Rejko UL; Muller, T.; Riess, O.

in Journal of neural transmission (Vienna, Austria : 1996) (2000), 107(1), 31-40

A major step in the elucidation of the pathogenesis of neurodegenerative disorders was the identification of a mutation in the alpha-synuclein gene in autosomal dominant Parkinson's disease (PD). Alpha ... [more ▼]

A major step in the elucidation of the pathogenesis of neurodegenerative disorders was the identification of a mutation in the alpha-synuclein gene in autosomal dominant Parkinson's disease (PD). Alpha-synuclein is the main component of Lewy bodies (LB), the neuropathological hallmark of PD. Moreover, a fragment of alpha-synuclein (NAC) is the second major component of amyloid plaques in Alzheimer's disease (AD). Recent studies of other neurodegenerative disorders such as dementia with LB (DLB), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS) also revealed intracellular accumulations of alpha-synuclein in affected brain regions. This may indicate that these disorders partially share common pathogenic mechanisms. Recent data provide first insights into the physiological function of alpha-synuclein and support the concept of an essential role of alpha-synuclein in neurodegeneration. Increasing knowledge on the pathogenic molecular mechanisms of neurodegeneration and of the pathophysiological function of alpha-synuclein in particular may influence future development of therapeutic strategies in neurodegenerative disorders. [less ▲]

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See detailGenetic analysis of the alpha2-macroglobulin gene in early- and late-onset Parkinson's disease.
Krüger, Rejko UL; Menezes-Saecker, A. M.; Schols, L. et al

in Neuroreport (2000), 11(11), 2439-42

Recent association studies investigating polymorphisms in the alpha2-macroglobulin (A2M) gene provided evidence for an involvement of this protease inhibitor in the pathogenesis of Alzheimer's disease (AD ... [more ▼]

Recent association studies investigating polymorphisms in the alpha2-macroglobulin (A2M) gene provided evidence for an involvement of this protease inhibitor in the pathogenesis of Alzheimer's disease (AD). The partially overlapping pathology between AD and Parkinson's disease (PD) led us to investigate the role of A2M in PD. We performed association studies in a large sample of 328 German PD patients and 322 closely matched healthy controls. Analyzing the Val1000Ile polymorphism and a pentanucleotide deletion in the 5' splice site of exon 18 of the A2M gene we found an excess of homozygosity for the A2M deletion in early-onset PD (EOPD) patients (age at onset < 50 years) compared to late-onset PD (LOPD) patients (age at onset > 50 years; p = 0.008, p(p)c = 0.064, chi2 = 7.017). Therefore our data might indicate an age at onset modulating effect of the homozygous A2M deletion in PD. [less ▲]

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See detailGenetic analysis of immunomodulating factors in sporadic Parkinson's disease.
Krüger, Rejko UL; Hardt, C.; Tschentscher, F. et al

in Journal of neural transmission (Vienna, Austria : 1996) (2000), 107(5), 553-62

Immunomodulating factors have been shown to play a role in the pathogenesis of Parkinson's disease (PD) by biochemical methods. In order to investigate functionally important genes of the tumor necrosis ... [more ▼]

Immunomodulating factors have been shown to play a role in the pathogenesis of Parkinson's disease (PD) by biochemical methods. In order to investigate functionally important genes of the tumor necrosis factor alpha (TNFalpha) pathway we studied the frequency of DNA polymorphisms in the interleukin 6 (IL6), the TNFalpha, and the TNFalpha receptor 1 (TNFR1) genes in 264 sporadic German PD patients and in 183 age and sex matched German healthy controls. Analyzing the TNFalpha-308 polymorphism we found heterozygous individuals carrying alleles 1 and 2 more frequently in patients with a relative risk of 1.56 (p = 0.046, p(c) = 0.13, chi2 = 3.98). In contrast, the frequency of the B/2 haplotype described by the TNFR1-609 and TNFRI+36 polymorphisms was significantly decreased in our PD patients group (p = 0.0097, p(c) = 0.048, chi2 = 6.69) with a relative risk reduced to 0.52. Our results suggest an involvement of immunomodulating factors in the pathogenesis of sporadic PD as revealed by a molecular genetic approach. [less ▲]

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See detailMutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients.
Wintermeyer, P.; Krüger, Rejko UL; Kuhn, W. et al

in Neuroreport (2000), 11(10), 2079-82

Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether ... [more ▼]

Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinson's disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI = 0.36-0.88; p = 0.012, p(c) = 0.047, chi2 = 6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration. [less ▲]

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See detailIncreased susceptibility to sporadic Parkinson's disease by a certain combined alpha-synuclein/apolipoprotein E genotype.
Krüger, Rejko UL; Vieira-Saecker, A. M.; Kuhn, W. et al

in Annals of neurology (1999), 45(5), 611-7

Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is ... [more ▼]

Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, alpha-synuclein (alpha-SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of alpha-SYN and apolipoprotein E, which is a major risk factor for late-onset Alzheimer's disease, prompted us to investigate the influence of different alpha-SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the alpha-SYN gene (NACP-Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apo epsilon4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early-onset PD patients (age at onset, <50 years) than in late-onset PD. Regarding the combination of the Apo epsilon4 allele and allele 1 of the alpha-SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8-fold increased relative risk for developing PD during their lives. [less ▲]

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See detailAnalysis of the parkin deletion in sporadic and familial Parkinson's disease. Short communication.
Krüger, Rejko UL; Vieira-Sacker, A. M.; Kuhn, W. et al

in Journal of neural transmission (Vienna, Austria : 1996) (1999), 106(2), 159-63

Recently a mutation in the parking gene has been identified as the cause for an autosomal-recessively inherited form of early onset Parkinson's disease (EOPD). The disease causing minimal deletion has ... [more ▼]

Recently a mutation in the parking gene has been identified as the cause for an autosomal-recessively inherited form of early onset Parkinson's disease (EOPD). The disease causing minimal deletion has been defined as a homozygous exon 4 loss in the parkin gene among Japanese patients. We investigated 140 sporadic and familial EOPD patients of German ancestry for the exon 4 deletion in the parkin gene. None of our patients exhibited a homozygous deletion of exon 4, suggesting a minor role of this mutation for EOPD in Caucasians. Nevertheless a detailed mutation analysis is warranted to explore the overall significance of mutations in the parkin gene in EOPD. [less ▲]

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See detailAla30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
Krüger, Rejko UL; Kuhn, W.; Muller, T. et al

in Nature genetics (1998), 18(2), 106-8

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See detailSelegiline as immunostimulant--a novel mechanism of action?
Muller, T.; Kuhn, W.; Krüger, Rejko UL et al

in Journal of neural transmission. Supplementum (1998), 52

In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The ... [more ▼]

In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain unclear. Several lines of evidence indicate an immune-mediated pathophysiology of PD and AD. According to animal trials, selegiline increases the survival rate of immune suppressed mice. Stimulation of the immune response to bacterial or viral infection or in chronic inflammatory processes in managed by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha (TNF). The aim of our study was to characterize the influence of selegiline on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood mononuclear cells (PBMC) from healthy blood donors. After isolation and washing PBMC were cultured without and with selegiline in three different concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7% CO2). Then cultures were centrifuged and supernatants were collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of selegiline on the cytokine biosynthesis may also contribute to its putative neuroprotective properties. [less ▲]

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See detailSelegiline stimulates biosynthesis of cytokines interleukin-1 beta and interleukin-6.
Wilfried, K.; Muller, T.; Krüger, Rejko UL et al

in Neuroreport (1996), 7(18), 2847-8

Several lines of evidence indicate an immune-mediated pathophysiology of Parkinson's disease (PD) and Alzheimer's disease (AD). In clinical studies the monoamine oxidase-B inhibitor Selegiline appears to ... [more ▼]

Several lines of evidence indicate an immune-mediated pathophysiology of Parkinson's disease (PD) and Alzheimer's disease (AD). In clinical studies the monoamine oxidase-B inhibitor Selegiline appears to slow the progression of neurological deficits in PD and the cognitive decline in AD. The immune response to bacterial or viral infection and in chronic inflammatory processes is stimulated by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequently interleukin-6 (IL-6). We investigated the influence of Selegiline on the synthesis of IL-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) from healthy blood donors cultured with or without Selegiline (10(-8)M, 10(-9)M or 10(-10)M) in a humidified atmosphere (7% CO2). Treatment of cultured PBMC with Selegiline significantly increased synthesis of both cytokines. The effect of Selegiline on cytokine biosynthesis may contribute to its putative neuroprotective properties. [less ▲]

Detailed reference viewed: 60 (2 UL)