0000000000650807
AUTHOR
Martin S. Weber
showing 4 related works from this author
Brain erythropoietin fine-tunes a counterbalance between neurodifferentiation and microglia in the adult hippocampus
2021
In adult cornu ammonis hippocampi, erythropoietin (EPO) expression drives the differentiation of new neurons,independent of DNA synthesis, and increases dendritic spine density. This substantial brain hardwareupgrade is part of a regulatory circle: during motor-cognitive challenge, neurons experience ‘‘functional’’hypoxia, triggering neuronal EPO production, which in turn promotes improved performance. Here, weshow an unexpected involvement of resident microglia. During EPO upregulation and stimulated neurodifferentiation,either by functional or inspiratory hypoxia, microglia numbers decrease. Treating mice with recombinanthuman (rh)EPO or exposure to hypoxia recapitulates these changes and…
CD14 is a key organizer of microglial responses to CNS infection and injury
2015
Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon β-mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced …
Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
2015
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK …
Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)
2021
Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particular…