A5078823006- RNA regulation and disease
- Immune Response and Inflammation
- Nuclear Receptors and Signaling
- T-cell and B-cell Immunology
- Ion Channels and Receptors
- interferon and immune responses
- Immunotherapy and Immune Responses
- Neurobiology and Insect Physiology Research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Macrophage Migration Inhibitory Factor
- Plant Stress Responses and Tolerance
- Genetics, Aging, and Longevity in Model Organisms
- Inflammasome and immune disorders
- Monoclonal and Polyclonal Antibodies Research
- MicroRNA in disease regulation
- Adenosine and Purinergic Signaling
Universität Hamburg
2022-2024
University Medical Center Hamburg-Eppendorf
2022-2024
Klinik und Poliklinik für Neurologie
2022
Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce stimulator interferon genes (STING). However, activation STING requires detachment from stromal interaction molecule 1 (STIM1), process triggered by glutamate excitotoxicity. This initiates non-canonical signaling, which leads to autophagic...
Neuroinflammation leads to neuronal stress responses that contribute dysfunction and loss. However, treatments stabilize neurons prevent their destruction are still lacking. Here, we identify the histone methyltransferase G9a as a druggable epigenetic regulator of vulnerability inflammation. In murine experimental autoimmune encephalomyelitis (EAE) human multiple sclerosis (MS), found G9a-catalyzed repressive mark H3K9me2 was robustly induced by neuroinflammation. activity repressed...
Migratory dendritic cells (migDCs) continuously patrol tissues and are activated by injury inflammation. Extracellular adenosine triphosphate (ATP) is released damaged or actively secreted during inflammation increases migDC motility. However, the underlying molecular mechanisms which ATP accelerates migration not understood. Here, we show that migDCs can be distinguished from other DC subsets immune their expression of voltage-gated calcium channel subunit β3 (Cavβ3; CACNB3), exclusively...
A disturbed balance between excitation and inhibition (E/I balance) is increasingly recognized as a key driver of neurodegeneration in multiple sclerosis (MS), chronic inflammatory disease the central nervous system. To understand how hyperexcitability contributes to neuronal loss MS, we transcriptionally profiled neurons from mice lacking inhibitory metabotropic glutamate signaling with shifted E/I increased vulnerability inflammation-induced neurodegeneration. This revealed prominent...
Differences in immune responses between women and men are leading to a strong sex bias the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests more than twice many making one most important risk factor. However, it is incompletely understood which genes contribute differences incidence. To address that, we conducted gene expression analysis female male human spleen identified transmembrane protein CD99 significantly differentially...
Neurodegeneration in central nervous system disorders is linked to dysregulated neuronal calcium. Direct inhibition of glutamate-induced calcium influx, particularly via N-methyl-D-aspartate receptors (NMDAR), has led adverse effects and clinical trial failures. A more feasible approach modulate NMDAR activity or signaling indirectly. In this respect, the calcium-activated non-selective cation channel transient receptor potential melastatin 4 (TRPM4) been identified as a promising target....
Two isogenic hiPSC lines, ZIPi013-B-1 and ZIPi013-B-2, were generated by CRISPR/Cas9-mediated indels in the TRPM4 gene of previously published ZIPi013-B. belongs to evolutionarily conserved family transient receptor potential (TRP) channels. It is expressed ubiquitously its activity regulated intracellular calcium binding, changes membrane potential, phosphoinositide lipids plasma local concentration cytoplasmic ATP ADP. has been implicated various diseases, including neurological immune...