A5070639742- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Phosphodiesterase function and regulation
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Chemical Synthesis and Analysis
University of Copenhagen
2015-2021
Monash University
2020-2021
Novo Nordisk (Denmark)
2020-2021
Inserm
2017
Université Paris-Sud
2017
Vrije Universiteit Amsterdam
2017
Inflammation, Microbiome and Immunosurveillance
2017
Université Paris-Saclay
2017
Abstract The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among most highly pursued drug targets, with relevance for several neurological diseases and number allosteric modulators entered clinical trials. However, so far this has not led to marketed drug, largely because difficulties achieving subtype-selective compounds desired properties. Very recently first crystal structures were published transmembrane domain two...
WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, which refers to abnormal accumulation of mature neutrophils in the bone marrow. The disease primarily caused by C-terminal truncation mutations chemokine receptor CXCR4, giving these CXCR4-WHIM mutants gain function response their ligand CXCL12. Considering broad functions CXCR4 maintaining leukocyte homeostasis, patients are...
Negative allosteric modulation of the metabotropic glutamate 5 (mGlu<sub>5</sub>) receptor has emerged as a potential strategy for treatment neurologic disorders. Despite success in preclinical studies, many mGlu<sub>5</sub> negative modulators (NAMs) that have reached clinical trials failed due to lack efficacy. In this study, we provide detailed vitro pharmacological characterization nine clinically and preclinically tested NAMs. We evaluated inhibition l-glutamate–induced signaling with...
Positive allosteric modulation of metabotropic glutamate subtype 5 (mGlu<sub>5</sub>) receptor has emerged as a potential new therapeutic strategy for the treatment schizophrenia and cognitive impairments. However, positive modulator (PAM) agonist activity been associated with adverse side effects, neurotoxicity also observed pure PAMs. The structural pharmacological basis versus mGlu<sub>5</sub> PAM in vivo effects remains unknown. Thus, gaining insights into signaling fingerprints, well...