A5074359060- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Folate and B Vitamins Research
- Neurological diseases and metabolism
- Autism Spectrum Disorder Research
- Nicotinic Acetylcholine Receptors Study
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Botulinum Toxin and Related Neurological Disorders
- Cell death mechanisms and regulation
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Metabolism and Genetic Disorders
- Restless Legs Syndrome Research
- Gut microbiota and health
University Hospital Bonn
2014-2025
German Center for Neurodegenerative Diseases
2016-2025
University of Bonn
2013-2024
Klinik und Poliklinik für Neurologie
2007-2022
Neurology, Inc
2014
Charité - Universitätsmedizin Berlin
2012
RWTH Aachen University
2011
Hertie Institute for Clinical Brain Research
2011
Goethe University Frankfurt
2011
Technische Universität Dresden
2011
Many neurodegenerative diseases are caused by intracellular, aggregate-prone proteins, including polyglutamine-expanded huntingtin in Huntington's disease (HD) and mutant tau fronto-temporal dementia/tauopathy. Previously, we showed that rapamycin, an autophagy inducer, enhances fragment clearance attenuated toxicity. Here show much wider applications for this approach. Rapamycin the autophagic of different proteins with long polyglutamines a polyalanine-expanded protein, reduces their also...
Parkinson's disease (PD) presently is conceptualized as a protein aggregation in which pathology involves both the enteric and central nervous system, possibly spreading from one to another via vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, system with its vast diversity of microorganisms may be involved PD pathogenesis. Alterations microbial taxonomic level L-DOPA-naïve patients might also serve biomarker. We performed metagenomic shotgun analyses...
There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study actually demonstrated that this modality administration increases concentrations peptide brain well blood humans. Here using combined cerebrospinal fluid (CSF) sampling subjects receiving either 24 IU (n = 11) or placebo 4) we have shown levels significantly increased both plasma CSF. However, whereas peaked at 15 min after decreased 75...
Alpha-synuclein ( SNCA ) is a major risk gene for Parkinson's disease (PD), and increased dosage results in parkinsonian syndrome affected families. We found that methylation of human intron 1 decreased expression, while inhibition DNA activated expression. Methylation was reduced from sporadic PD patients' substantia nigra, putamen, cortex, pointing toward yet unappreciated epigenetic regulation expression PD.
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
Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement GI tract and enteric nervous system highlights need for better understanding role gut microbiota in complications PD. Here, we investigate microbiome patients with PD using metagenomics serum metabolomics. We integrate these data metabolic modeling...
Abstract To study the putative association of dopamine agonists with sleep attacks in patients Parkinson's disease (PD) and their relation to daytime sleepiness, we performed a survey 2,952 PD two German counties. In 177 patients, sudden, unexpected, irresistible episodes while engaged some activity were identified structured telephone interview. Ninety‐one these denied occurrence appropriate warning signs. A total 133 (75%) had an Epworth Sleepiness Scale (ESS) score >10; 65 (37%)...
Abstract α‐Synuclein is considered to play an important role in the pathogenesis of both rare familial and common sporadic forms Parkinson's disease. Previous reports primarily have tested association α‐synuclein promoter polymorphisms with idiopathic disease, but results are controversial. We first characterized linkage disequilibrium structure gene region a dense set 56 genetic markers subsequently performed two independent case–control analyses using tagging markers. could distinguish...
Abstract: Exposure of neuronal PC12 cells, differentiated by nerve growth factor, to tumor necrosis factor‐α (TNF‐α) and bacterial lipopolysaccharide (LPS) resulted in de novo synthesis inducible nitric oxide synthase (iNOS) mRNA protein with an increase up 24 h. Brain NOS expression was unaffected. The induction iNOS differntiated cells associated cell death characterized features apoptosis, inhibitors N ‐monomethylarginine, aminoguanidine, 2‐amino‐5,6‐dihydro‐6‐methyl‐4 H ‐1,3‐thiazine HCl...
<h3>Objective:</h3> To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook genome-wide association study (GWAS). <h3>Methods:</h3> We performed GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) 918 patients MSA European ancestry 3,864 controls. cases were collected from North American centers, one third which neuropathologically confirmed. <h3>Results:</h3> found no significant loci after stringent...
Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that characterized by the intracellular accumulation of alpha-synuclein containing aggregates. Recent increasing evidence suggests MSA pathology spread throughout nervous in a spatiotemporal fashion, possibly prion-like propagation positive aggregates between synaptically connected areas. Concurrently, intracerebral injection pathological into transgenic mice overexpressing human wild-type...
A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic semantic memory, motor coordination. Severity was assessed with the Scale for Assessment Rating Ataxia (SARA), nonataxia symptoms Inventory Non-Ataxia Symptoms. Depressive were evaluated Beck Depression...
Background Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or A53T missense mutation of presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically preferential vulnerability dopaminergic nigrostriatal projection neurons. Methodology/Principal Findings Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in absence neurodegeneration to understand early...
Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson (PD) and dementia Lewy bodies (DLB). To investigate the role of GBA in multiple system atrophy (MSA), we analyzed a large case-control series.We sequenced coding regions flanking splice sites 969 MSA patients (574 Japanese, 223 European, 172 North American) 1509 control subjects (900 315 294 American). We focused solely on Gaucher-disease-causing variants.In Japanese series, found nine carriers...
Neurodegenerative diseases (NDD) such as Alzheimer's (AD) and Parkinson's disease (PD) are distinct clinical entities, however, the aggregation of key neuronal proteins, presumably leading to demise appears represent a common mechanism. It has become evident, that advanced glycation end products (AGEs) trigger accumulation modified which eventually contributes pathological aspect NDDs. Increased levels AGEs found in amyloid plaques AD brains both early PD (incidental Lewy body disease). The...