A5059545769- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Ubiquitin and proteasome pathways
- Advanced Fluorescence Microscopy Techniques
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Nerve injury and regeneration
- Cell Image Analysis Techniques
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Spectroscopy and Chemometric Analyses
- Connexins and lens biology
- RNA regulation and disease
- Blind Source Separation Techniques
- Erythrocyte Function and Pathophysiology
- Stress Responses and Cortisol
- Neuroscience and Neural Engineering
- Biochemical effects in animals
- Adenosine and Purinergic Signaling
- Adolescent and Pediatric Healthcare
- Protein Degradation and Inhibitors
Max Planck Institute for Multidisciplinary Sciences
2022-2024
Max Planck Institute of Experimental Medicine
2013-2022
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2009-2013
Deutsche Forschungsgemeinschaft
2009-2010
Max Planck Institute for Biophysical Chemistry
2003
University of Wyoming
2003
Keeping cholesterol at bay A decline in tissue repair is a universal hallmark of aging. The failure to regenerate myelin sheaths multiple sclerosis lesions contributes chronic progressive disease and disability. Understanding the cause preventing this key goal regenerative medicine. Cantuti-Castelvetri et al. report that self-limiting inflammatory response, which necessary for remyelination occur, maladaptive central nervous system (CNS) old mice (see Perspective by Chen Popko)....
Neuron–glia interactions play a key role in maintaining and regulating the central nervous system. Glial cells are implicated function of dopamine neurons regulate their survival resistance to injury. Parkinson's disease is characterized by loss substantia nigra pars compacta, decreased striatal levels consequent onset extrapyramidal motor dysfunction. common chronic, neurodegenerative disorder with no effective protective treatment. In 6‐OHDA mouse model disease, doxycycline administered at...
Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression bipolar disease. This consistent EPO effect on cognition is independent of its role hematopoiesis. The cellular mechanisms action brain, however, have remained unclear. Here we studied healthy young mice observed that 3-week administration was associated with an increased number pyramidal neurons oligodendrocytes the...
To maintain homeostasis, the body, including brain, reprograms its metabolism in response to altered nutrition or disease. However, consequences of these challenges for energy different brain cell types remain unknown. Here, we generated a proteome atlas major central nervous system (CNS) from young and adult mice, after feeding therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) during neuroinflammation. Under steady-state conditions, CNS prefer distinct modes...
Pelizaeus–Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood–brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary two patients did not lead major advancement hypomyelination, potentially because intact precludes its entry into CNS. We therefore turned preserved integrity high-fat/low-carbohydrate ketogenic diet restored oligodendrocyte increased...
Reactive oxygen species (ROS) are emerging as important regulators of cancer growth and metastatic spread. However, how cells integrate redox signals to affect progression is not fully understood. Mitochondria cellular hubs, which highly regulated by interactions with neighboring organelles. Here, we investigated ROS at the endoplasmic reticulum (ER)-mitochondria interface generated translated melanoma outcome. We show that TMX1 TMX3 oxidoreductases, promote ER-mitochondria communication,...
Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s core AZ with an essential function in SV priming. In hippocampal neurons, two different Munc13s-Munc13-1 bMunc13-2-mediate opposite forms presynaptic short-term plasticity thus differentially affect characteristics. We found most presynapses cortical neurons only Munc13-1, whereas ∼10%...
A modern day light microscope has evolved from a tool devoted to making primarily empirical observations what is now sophisticated , quantitative device that an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use capturing quantifying scientific phenomena, neither thorough understanding the principles underlying imaging techniques nor appropriate knowledge how calibrate,...
Abstract During myelin formation, vast amounts of specialized membrane proteins and lipids are trafficked toward the growing sheath in cell surface‐directed transport vesicles. Soluble N‐ethylmaleimide‐sensitive factor (NSF) attachment (SNAPs) important components molecular complexes required for fusion. We have analyzed expression profile interactions SNAP‐29 nervous system. In addition to its known enrichment neuronal synapses, is abundant oligodendrocytes during myelination noncompact...
Inflammatory mechanisms are proposed to play a role in L-DOPA-induced dyskinesia. Cyclooxygenase-2 (COX2) contributes inflammation pathways the periphery and is constitutively expressed central nervous system. Considering that inhibition of nitric oxide (NO) formation attenuates dyskinesia, this study aimed at investigating if NO synthase (NOS) inhibitor would change COX2 brain expression animals with To aim, male Wistar rats received unilateral 6-hydroxydopamine microinjection into medial...
Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) fluorescent quantum dots (QDs) for single- two-photon imaging human in ex vivo biological samples breast pancreatic metastatic mouse models expressing epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen...
The ability of somatosensory neurons to perceive mechanical stimuli relies on specialized mechanotransducing proteins and their molecular environment. Only recently has the identity a major transducer forces in vertebrates been revealed by discovery Piezo2. Further work established its pivotal role for innocuous touch mice. Therefore, Piezo2 offers unique platform investigation mechanosensation. We performed mass spectrometry-based interactomics screen native mouse dorsal root ganglia (DRG)....
Store-operated calcium entry (SOCE) through STIM-gated ORAI channels governs vital cellular functions. In this context, SOCE controls redox signaling and is itself regulated by modifications. However, the molecular mechanisms underlying calcium-redox interplay functional outcomes are not fully understood. Here, we examine role of STIM2 in regulation. Redox proteomics identify cysteine 313 as main sensor vitro vivo. Oxidative stress suppresses currents cells overexpressing ORAI1, an effect...
SUMOylation is an evolutionarily conserved eukaryotic posttranslational protein modification with broad biological relevance. Differentiating between the major small ubiquitin-like modifier (SUMO) paralogs and uncovering paralog-specific functions in vivo has long been very difficult. To overcome this problem, we generated His6-HA-Sumo2 HA-Sumo2 knockin mouse lines, expanding upon our existing His6-HA-Sumo1 line, to establish a "toolbox" for Sumo1-Sumo2 comparisons vivo. Leveraging...
Pancreatic ductal adenocarcinoma (PDAC) progresses in an organ with a unique pH landscape, where the stroma acidifies after each meal. We hypothesized that disrupting this landscape during PDAC progression triggers pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) to induce fibrosis. revealed alkaline environmental was sufficient PSC differentiation myofibroblastic phenotype. then mechanistically dissected finding, focusing on involvement of Na+/H+ exchanger NHE1....
Nitric oxide is unconstrained by cell membranes and can therefore act along a broad distance as volume transmitter. Spillover of nitric between neurons may have major impact on central nervous system diseases particularly neurodegeneration. There evidence whereby communication nitrergic dopaminergic systems plays an essential role in the control nigrostriatal pathway. However, there sparse information for either coexistence or overlap structures. The present study used double-labeling...
Abnormalities and impairments in axonal transport are suggested to strongly contribute the pathological alterations underlying AD. The exact mechanisms leading axonopathy currently unclear, but it was recently that APP expression itself triggers degeneration. We used transgenic mice crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Depending mutant dosage, we demonstrate clear aggravation both plaque-associated plaque-distant degeneration, despite of an unchanged...
Molecular imaging of inflammatory lung diseases, such as asthma, has been limited to date. The recruitment innate immune cells the airways is central inflammation process. This study exploits these for purposes within lung, using inhaled polystyrene nanoparticles loaded with near-infrared fluorescence dye Itrybe (Itrybe-NPs). By means in vivo and ex reflectance an ovalbumin-based allergic airway (AAI) model hairless SKH-1 mice, we show that subsequent intranasal application Itrybe-NPs, AAI...