A5067791805- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Cellular transport and secretion
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Trace Elements in Health
- Congenital heart defects research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- S100 Proteins and Annexins
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Traumatic Brain Injury and Neurovascular Disturbances
- Ion channel regulation and function
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Hippo pathway signaling and YAP/TAZ
- Parkinson's Disease Mechanisms and Treatments
- Lipid Membrane Structure and Behavior
- CRISPR and Genetic Engineering
Universität Ulm
2016-2025
German Center for Neurodegenerative Diseases
2019-2025
Helmholtz-Institute Ulm
2020-2023
Technologie- und Förderzentrum
2019-2022
Institute for Molecular Medicine
2021
Institute for Neurodegenerative Disorders
2020
University of Turin
2016
Institute of Cell Biology and Neurobiology
2012
University of Tübingen
2012
Life & Brain (Germany)
2010
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental with complex inheritance pattern. While many rare variants in synaptic proteins have been identified patients ASD, little is known about their effects at the synapse and interactions other genetic variations. Here, following discovery two de novo SHANK2 deletions by Genome Project, we novel 421 kb deletion patient autism. We then sequenced 455 ASD 431 controls integrated these results those reported Berkel et al....
Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Cytoplasmic fused in sarcoma (FUS) aggregates are pathological hallmarks of FUS-ALS. Proper shuttling between nucleus and cytoplasm essential for physiological cell function. However, initial event pathophysiology FUS-ALS remains enigmatic. Using human induced pluripotent stem (hiPSCs)-derived neurons (MNs), we show that impairment poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response (DDR) signaling...
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...
Abstract Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) can restrict viral pathogens, but pro- anti-viral activities have been reported for coronaviruses. Here, we show that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. However, endogenous IFITM expression supports efficient infection in human lung cells. Our results indicate the Spike protein interacts with hijacks them were expressed further induced by interferons lung, gut, heart brain IFITM-derived...
The postsynaptic density (PSD) is a complex assembly of proteins associated with the membrane that organizes neurotransmitter receptors, signaling pathways, and regulatory elements within cytoskeletal matrix. Here we show sterile alpha motif domain rat Shank3/ProSAP2, master scaffolding protein located deep PSD, can form large sheets composed helical fibers stacked side by side. Zn 2+ , which found in high concentrations binds tightly to Shank3 may regulate assembly. Sheets Shank could...
The postsynaptic density (PSD) is crucially involved in the structural and functional organization of neurotransmitter reception apparatus. Using antisera against rat brain synaptic junctional protein preparations, we isolated cDNAs coding for proline-rich synapse-associated protein-1 (ProSAP1), a PDZ-domain protein. This was found to be identical recently described cortactin-binding (CortBP1). Homology screening identified related protein, ProSAP2. Specific raised C-terminal fusion...
Neurocan is a component of the extracellular matrix in brain. Due to its inhibition neuronal adhesion and outgrowth vitro expression pattern vivo it was suggested play an important role axon guidance neurite growth. To study neurocan brain development we generated neurocan-deficient mice by targeted disruption gene. These are viable fertile have no obvious deficits reproduction general performance. Brain anatomy, morphology, ultrastructure similar those wild-type mice. Perineuronal nets...
NMDA (N-methyl-D-aspartate) receptors and calcium can exert multiple very divergent effects within neuronal cells, thereby impacting opposing occurrences such as synaptic plasticity degeneration. The Ca2+ sensor Caldendrin is a postsynaptic density component with high similarity to calmodulin. Jacob, recently identified binding partner, novel protein abundantly expressed in limbic brain cerebral cortex. Strictly depending upon activation of NMDA-type glutamate receptors, Jacob recruited...
Recent studies suggest that central nervous system synapses can persist for weeks, months, perhaps lifetimes, yet little is known as to how maintain their structural and functional characteristics so long. As a step toward better understanding of synaptic maintenance we examined the loss, redistribution, reincorporation, replenishment dynamics Synapsin I ProSAP2/Shank3, prominent presynaptic postsynaptic matrix molecules, respectively. Fluorescence recovery after photobleaching...
Mutations in several postsynaptic proteins have recently been implicated the molecular pathogenesis of autism and spectrum disorders (ASDs), including Neuroligins, Neurexins, members ProSAP/Shank family, thereby suggesting that these genetic forms may share common synaptic mechanisms. Initial studies ASD-associated mutations ProSAP2/Shank3 support a role for this protein glutamate receptor function spine morphology, but phenotypes are not universally penetrant, indicating other core facets...
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...
Article6 June 2018Open Access Source DataTransparent process NF-κB activation in astrocytes drives a stage-specific beneficial neuroimmunological response ALS Najwa Ouali Alami Department of Neurology, Ulm University, Ulm, Germany Search for more papers by this author Christine Schurr Institute Physiological Chemistry, Florian Olde Heuvel Linyun Tang Qian Li orcid.org/0000-0002-6621-2167 Alpaslan Tasdogan Immunology, Atsushi Kimbara Roche Pharma Research and Early Development, Innovation...
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...