A5087839683- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Biomedical and Chemical Research
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Noise Effects and Management
- Renal Diseases and Glomerulopathies
- RNA Research and Splicing
- Ion Transport and Channel Regulation
- Neurogenesis and neuroplasticity mechanisms
- Retinal Development and Disorders
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
- ATP Synthase and ATPases Research
- Anatomy and Medical Technology
- Nerve injury and regeneration
- History of Medical Practice
- Trace Elements in Health
- Photoreceptor and optogenetics research
University Medical Center of the Johannes Gutenberg University Mainz
2020-2025
Johannes Gutenberg University Mainz
2020-2025
Focus (Germany)
2020-2025
Leibniz Institute for Neurobiology
2017-2020
Universität Ulm
2009-2018
Otto-von-Guericke University Magdeburg
2017-2018
University of Turin
2016
Abstract Loss-of-function mutations in the gene encoding postsynaptic scaffolding protein SHANK2 are a highly penetrant cause of autism spectrum disorders (ASD) involving cerebellum-related motor problems. Recent studies have implicated cerebellar pathology aetiology ASD. Here we evaluate possibility that Purkinje cells (PCs) represent critical locus ASD-like pathophysiology mice lacking Shank2 . Absence impairs both PC intrinsic plasticity and induction long-term potentiation at parallel...
Proteins of the ProSAP/Shank family act as major organizing scaffolding elements within postsynaptic density excitatory synapses. Deletions, mutations or downregulation these molecules has been linked to autism spectrum disorders, related Phelan McDermid Syndrome Alzheimer's disease. proteins are targeted synapses depending on binding zinc, which is a prerequisite for assembly scaffold. To gain insight into whether previously reported through zinc ions provides crossing point between genetic...
Alterations of learning and memory in mice with deregulated neuron-specific nuclear factor κB (NF-κB) activity support the idea that plastic changes synaptic contacts may depend at least part on IκB kinase (IKK)/NF-κB-related synapse-to-nucleus signaling. There is, however, little information molecular requirements mechanisms regulating this IKK/NF-κB-dependent synapse development remodeling. Here, we report NF-κB inducing IKK complex is localized postsynaptic density (PSD) activated under...
Located at neuronal terminals, the postsynaptic density (PSD) is a highly complex network of cytoskeletal scaffolding and signaling proteins responsible for transduction modulation glutamatergic between neurons. Using ion-mobility enhanced data-independent label-free LC-MS/MS, we established reference proteome crude synaptosomes, synaptic junctions, PSD derived from mouse hippocampus including TOP3-based absolute quantification values identified proteins. The final dataset across all...
Fused in Sarcoma (FUS) is a multifunctional RNA-/DNA-binding protein, which involved the pathogenesis of neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A common hallmark these abnormal accumulation mutated FUS protein cytoplasm. Under normal conditions confined to nuclear compartment, neurons, however, additional somatodendritic localization can be observed. In this study, we carefully analyzed subcellular endogenous at synaptic sites...
Disruption of the human SHANK3 gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome (PMS), autism spectrum disorder (ASD) and intellectual disability (ID). Although a wide array neurobiological studies strongly supports major role for in organizing postsynaptic protein scaffold, molecular processes at synapses individuals harboring mutations are still far from being understood. In this study, we biochemically isolated density (PSD) fraction striatum...
Large epidemiological studies have shown that traffic noise promotes the development of cardiometabolic diseases. It remains to be established how long these adverse effects may persist in response a noise-off period. We investigated acute aircraft exposure (mean sound level 72 dB(A) applied for 4d) on oxidative stress and inflammation mediating vascular dysfunction increased blood pressure male C57BL/6 J mice. 1, 2 or 4d cessation after continuous period completely normalized noise-induced...
Memory deficits in Alzheimer's disease (AD) manifest together with the loss of synapses caused by disruption postsynaptic density (PSD), a network scaffold proteins located dendritic spines. However, underlying molecular mechanisms remain elusive. Since it was shown that ProSAP2/Shank3 assembly within PSD is Zn2+-dependent and amyloid beta protein (Aβ) able to bind Zn2+, we hypothesize sequestration Zn2+ ions Aβ contributes ProSAP/Shank platform malformation.To test this hypothesis, designed...
SHANK proteins are crucial for the formation and plasticity of excitatory synapses. Although mutations in all three genes associated with autism spectrum disorder (ASD), SHANK3 appears to be major ASD gene a prevalence approximately 0.5% ASD, higher rates individuals intellectual disability (ID). Interestingly, most relevant typically de novo often frameshift or nonsense resulting premature stop truncation protein.We analyzed different that we identified and/or ID, one novel (c.5008A > T)...
Ion fluxes across the inner mitochondrial membrane control volume, energy production, and apoptosis. TMBIM5, a highly conserved protein with homology to putative pH-dependent ion channels, is involved in maintenance of cristae architecture, ATP Here, we demonstrate that overexpressed TMBIM5 can mediate calcium uptake. Under steady-state conditions, loss results increased potassium reduced proton levels matrix caused by attenuated exchange these ions. To identify vivo consequences...
Background The stabilization or regulated reorganization of the actin cytoskeleton is essential for cellular structure and function. Recently, we could show that activation SK3-channel represents predominant SK-channel in neural stem cells, leads to a rapid local outgrowth long filopodial processes. This observation indicates rearrangement based via membrane bound SK3-channels might selectively be controlled defined micro compartments cell. Principal Findings We found two important proteins...
Abstract Autism‐related Shank1, Shank2, and Shank3 are major postsynaptic scaffold proteins of excitatory glutamatergic synapses. A few studies, however, have already indicated that within a neuron, the presence Shank family members is not limited to density. By separating axons from dendrites developing hippocampal neurons in microfluidic chambers, we show RNA all three present axons. Immunostaining confirms these findings as Shanks indeed found separated further co‐localize with well‐known...
Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance in mice response to chronic exposure. C57BL/6J were exposed aircraft 0, 4, 7, 14 28d at a mean sound pressure level of 72 dB(A) peak levels 85 dB(A). Chronic exposure up caused persistent dysfunction elevation blood pressure. Likewise, reactive oxygen...