A5063444804- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Neurological diseases and metabolism
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Ubiquitin and proteasome pathways
- Nerve injury and regeneration
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Hereditary Neurological Disorders
- Molecular Biology Techniques and Applications
- Autism Spectrum Disorder Research
- Prenatal Screening and Diagnostics
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
University of Tübingen
2016-2025
Universitätsklinikum Tübingen
2005-2024
Bernstein Center for Computational Neuroscience Tübingen
2004-2024
Charité - Universitätsmedizin Berlin
1986-2023
Hertie Institute for Clinical Brain Research
2004-2023
Hôpital Gui de Chauliac
2023
University Hospital Bonn
2023
ZB MED - Information Centre for Life Sciences
2023
Ludwig-Maximilians-Universität München
2023
German Center for Neurodegenerative Diseases
2023
Fast and reliable detection of patients with severe heterogeneous illnesses is a major goal precision medicine1,2. Patients leukaemia can be identified using machine learning on the basis their blood transcriptomes3. However, there an increasing divide between what technically possible allowed, because privacy legislation4,5. Here, to facilitate integration any medical data from owner worldwide without violating laws, we introduce Swarm Learning-a decentralized machine-learning approach that...
Recently targeted disruption of Omi/HtrA2 has been found to cause neurodegeneration and a parkinsonian phenotype in mice. Using candidate gene approach, we performed mutation screening the German Parkinson's disease (PD) patients. In four patients, identified novel heterozygous G399S mutation, which was absent healthy controls. Moreover, A141S polymorphism that associated with PD (P<0.05). Both mutations resulted defective activation protease activity Omi/HtrA2. Immunohistochemistry...
Background Mitochondrial dysfunction and degradation takes a central role in current paradigms of neurodegeneration Parkinson's disease (PD). Loss DJ-1 function is rare cause familial PD. Although critical oxidative stress response mitochondrial has been recognized, the effects on dynamics downstream consequences remain to be determined. Methodology/Principal Findings Using loss cellular models from knockout (KO) mice human carriers E64D mutation gene we define novel integrity both...
Abstract To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed candidate single nucleotide polymorphism (SNP) association study of 384 most associated SNPs in genome‐wide 413 MSA cases 3,974 control subjects. The 10 significant were then replicated additional 108 537 controls. at SNCA locus significantly with risk for increased development (combined p = 5.5 × 12 ; odds ratio 6.2). Ann Neurol 2009;65:610–614
The conversion of endogenous alpha-synuclein (asyn) to pathological asyn-enriched aggregates is a hallmark Parkinson's disease (PD). These inclusions can be detected in the central and enteric nervous system (ENS). Moreover, gastrointestinal symptoms appear up 20 years before diagnosis PD. dual-hit hypothesis posits that asyn aggregation starts ENS, retrogradely spreads brain. In this study, we tested by directly injecting preformed fibrils into duodenum wall wild-type rats transgenic with...
Background and Purpose— Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease young adults. Although risk factors manifestation atherosclerosis are commonly associated with stroke elderly, recent data suggests different causes for young. We initiated prospective, multinational European study Stroke Young Fabry Patients (sifap) to characterize a cohort patients. Methods—...
α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings cellular pathologies associated still elusive, complicating development effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational...
Neuroinflammation is one of the hallmarks Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, effects stimulating resolution in PD - modulate progression still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA properties, reduced...
In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories the implementation and accreditation of NGS a setting. These mainly focused on Whole Exome (WES) targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) insertions/deletions (indels)). Since then, Genome (WGS) has increasingly introduced diagnosis rare diseases as WGS allows simultaneous detection SNVs,...
The aim of the present study was (i) to compare disease progression and survival in different types degenerative ataxia, (ii) identify variables that may modify rate progression. We included patients suffering from Friedreich's ataxia (FRDA, n = 83), early onset cerebellar (EOCA, 30), autosomal dominant (ADCA) type I (ADCA-I, 273), ADCA-III (n 13) multiple system atrophy (MSA, 67). Molecular genetic testing allowed us assign 202 ADCA-I one following subgroups: spinocerebellar (SCAI, 36),...
Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of CAG trinucleotide repeat more than 39 units gene unknown function. Several mouse models have been reported which show rapid progression phenotype leading to death within 3–5 months (transgenic models) resembling the rare juvenile course HD (Westphal variant) or do not present with any symptoms (knock-in mice). Owing small size brain, mice are suitable for repetitive vivo imaging...
Abstract Seventy‐seven families with autosomal dominant cerebellar ataxia were analyzed for the CAG repeat expansions causing spinocerebellar (SCA) types 1, 2, 3, and 6. The SCA1 mutation accounted 9%, SCA2 10%, SCA3 42%, SCA6 22% of German families. Seven 27 patients had no family history ataxia. Age at onset correlated inversely length in all subtypes. Yet average effect one unit on age was different each SCA subtype. We compared clinical, electrophysiological, magnetic resonance imaging...
Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% Western populations older than age 50. The pathological hallmark PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons substantia nigra. Recently, alpha-synuclein (alpha-SYN) has been identified as main component sporadic PD, suggesting involvement neurodegeneration via protein accumulation. partially overlapping pathology and Alzheimer's disease, well striking...
Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of polyglutamine repeat region within ataxin-3 protein. The mutant protein forms intracellular aggregates in brain. However, cellular mechanisms causing toxicity are still poorly understood and there currently no effective treatments. In this study we show that administration rapamycin ester (cell cycle inhibitor-779, temsirolimus) improves motor performance transgenic mouse model spinocerebellar 3....