A5058152094- Hereditary Neurological Disorders
- Peripheral Neuropathies and Disorders
- Nerve injury and regeneration
- Signaling Pathways in Disease
- Botulinum Toxin and Related Neurological Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
- Homicide, Infanticide, and Child Abuse
- Histone Deacetylase Inhibitors Research
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Corporate Governance and Management
- Plant Disease Resistance and Genetics
- Toxin Mechanisms and Immunotoxins
- Plant Pathogens and Resistance
- Viral Infections and Immunology Research
- Healthcare Policy and Management
- Sphingolipid Metabolism and Signaling
- Mitochondrial Function and Pathology
- Chromosomal and Genetic Variations
- Neurogenetic and Muscular Disorders Research
- Insect and Pesticide Research
- Herpesvirus Infections and Treatments
- Lysosomal Storage Disorders Research
Universitätsklinikum Würzburg
2015-2024
Wageningen University & Research
2023
University of Würzburg
2010-2016
Bipar
2013
University of Iowa
2004-2010
Iowa Department of Public Health
2010
Illinois Department of Public Health
2010
Hygienic Research Institute (India)
2010
Laboratoire des Sciences de l’Information et de la Communication
2010
University of Iowa Hospitals and Clinics
2010
Abstract Eosinophil recruitment and enhanced production of NO are characteristic features asthma. However, neither the ability eosinophils to generate NO-derived oxidants nor their role in nitration targets during asthma is established. Using gas chromatography-mass spectrometry we demonstrate a 10-fold increase 3-nitrotyrosine (NO2Y) content, global marker protein modification by reactive nitrogen species, proteins recovered from bronchoalveolar lavage severe asthmatic patients (480 ± 198...
In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit developmental defect includes reduced transcription genes required for myelin lipid biosynthesis. Consequently, incorporation into is reduced, leading to an overall distorted stoichiometry proteins lipids...
See Scherer (doi:10.1093/awv279) for a scientific commentary on this article. Charcot–Marie–Tooth type 1 neuropathies are inherited disorders of the peripheral nervous system caused by mutations in Schwann cell-related genes. Typically, no causative cure is presently available. Previous preclinical data our group highlight low grade, secondary inflammation common to distinct as disease amplifier. In current study, we have tested one several available clinical agents targeting macrophages...
Aging is known as a major risk factor for the structure and function of nervous system. There urgent need to overcome such deleterious effects age-related neurodegeneration. Here we show that peripheral nerves 24-month-old aging C57BL/6 mice either sex similar pathological alterations from human individuals, whereas 12-month-old adult lack alterations. Specifically, nerve fibers showed demyelination, remyelination axonal lesion. Moreover, in mice, neuromuscular junctions features typical...
We investigated connexin 32 (Cx32)‐deficient mice, a model for the X‐linked form of Charcot‐Marie‐Tooth neuropathy (CMT1X), regarding impact low‐grade inflammation on Schwann cell phenotype. Whereas we previously identified macrophages as amplifiers neuropathy, now explicitly focus phagocytes dedifferentiation, so far not‐yet addressed disease‐related mechanism CMT1X. Using mice heterozygously deficient Cx32 and displaying both Cx32‐positive ‐negative cells in one same nerve, could...
We investigated three models for Charcot–Marie–Tooth type 1 (CMT1) neuropathy, comprising mice lacking connexin 32 (Cx32def), with reduced myelin protein zero (P0) expression (P0het) and transgenic mouse mutants overexpressing peripheral 22 (PMP22tg), regard of the developmentally regulated molecules NCAM, L1, low-affinity NGF-receptor p75 (p75NTR) transcription factor component c-Jun. found that all were uniformly expressed by deficient supernumerary Schwann cells. The mutant myelinating...
Purpose: Prescription medication use is essential to the health and well-being of many elderly persons. However, cost medications may be prohibitive contribute noncompliance with medical recommendations. This study identifies community-dwelling elders who reported a delay in because prescription cost. Design Methods: was cross-sectional nationwide sample 6,535 participating Asset Health Dynamics Among Oldest Old (AHEAD) study. Participants if they had taken less than prescribed or not filled...
Isolated generalized dystonia is a central motor network disorder characterized by twisted movements or postures. The most frequent genetic cause GAG deletion in the Tor1a (DYT1) gene encoding torsinA with reduced penetrance of 30-40 % suggesting additional environmental modifiers. Development dystonia-like after standardized peripheral nerve crush lesion wild type (wt) and Tor1a+/- mice, that express 50 only, was assessed scoring hindlimb during tail suspension, rotarod testing...
Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, found PLP overexpression in oligodendrocytes led to significantly reduced transport retina ganglion cell axons. We also observed an accumulation of mitochondria juxtaparanodal swellings, indicative for disturbed...
Abstract Genetically caused neurological disorders of the central nervous system (CNS) usually result in poor or even fatal clinical outcome and few no causative treatments are available. Often, these associated with disease‐amplifying neuroinflammation, a feature shared by progressive forms multiple sclerosis (PMS), another poorly treatable disorder CNS. We have previously generated two mouse lines carrying distinct mutations oligodendrocytic PLP1 gene that initially been identified...
Myelin protein zero mutations were found to produce Charcot–Marie–Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form severe early onset forms. Protein deficient homozygous mice () show a progressive dysmyelinating neuropathy birth compromised compaction, hypomyelination distal degeneration. A previous study using immunofluorescence showed that motor nerves upregulate NaV1.8 voltage gated sodium channel...
Abstract We have previously shown that targeting endoneurial macrophages with the orally applied CSF‐1 receptor specific kinase (c‐FMS) inhibitor PLX5622 from age of 3 months onwards led to a substantial alleviation neuropathy in mouse models Charcot‐Marie‐Tooth (CMT) 1X and 1B disease, which are genetically‐mediated nerve disorders not treatable humans. The same approach failed model CMT1A (PMP22‐overexpressing mice, line C61), representing most frequent form CMT. This was unexpected since...
Abstract Background and Aims The complex cellular molecular interactions between Schwann cells (SCs) macrophages during Wallerian degeneration are a prerequisite to allow rapid uptake degradation of myelin debris axonal regeneration after peripheral nerve injury. In contrast, in non‐injured nerves Charcot‐Marie‐Tooth 1 neuropathies, aberrant macrophage activation by SCs carrying gene defects is disease amplifier that drives damage subsequent functional decline. Consequently, targeting might...
The balanced segregation of homologous chromosomes during meiosis is essential for fertility and mediated by crossovers (COs). A strong reduction CO number leads to the unpairing after withdrawal synaptonemal complex. This results in random univalents I ultimately production unbalanced sterile gametes. However, if shortage combined with another meiotic alteration that restitutes first division, then uniform unreduced male gametes, essentially composed nonrecombinant homologs, are produced....
We could previously identify components of both the innate and adaptive immune system as disease modifiers in pathogenesis models for Charcot-Marie-Tooth (CMT) neuropathies type 1B 1X. As part system, here we investigated role antibodies a model CMT1B. Antibodies were localized characterized peripheral nerves CMT1B by immunohistochemistry Western blot analysis. Experimental ablation was performed cross breeding with mutants deficient B-lymphocytes (JHD−/− mutants). Ameliorated demyelination...