A5053568782- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Medical Imaging Techniques and Applications
- Radiopharmaceutical Chemistry and Applications
- Cannabis and Cannabinoid Research
- Adenosine and Purinergic Signaling
- Cholinesterase and Neurodegenerative Diseases
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and Biological Evaluation
- Advanced Glycation End Products research
- Ion channel regulation and function
- Phosphodiesterase function and regulation
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Phenothiazines and Benzothiazines Synthesis and Activities
- Neurotransmitter Receptor Influence on Behavior
- Lanthanide and Transition Metal Complexes
- Adipose Tissue and Metabolism
- Computational Drug Discovery Methods
- Click Chemistry and Applications
Helmholtz-Zentrum Dresden-Rossendorf
2016-2025
Institute of Cancer Research
2015-2021
Institut für Nichtklassische Chemie
2006-2009
Friedrich Schiller University Jena
2000-2008
Fraunhofer Institute for Cell Therapy and Immunology
2001-2003
Abstract Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype the offspring induced MIA, as microglia have key roles development and maintenance neuronal signaling central nervous system. The beneficial effects immunomodulatory treatment with minocycline on schizophrenic patients are consistent this hypothesis. Using MIA mouse model, we found...
The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal 18F-FDG PET/MRI was performed effects hypo- hyperthyroidism BAT mass activity. Ex-vivo14C-acetate loading assay assessment thermogenic gene protein expression permitted analysis oxidative capacities WAT...
In early Alzheimer's dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid predict further decline and neurodegeneration. Amyloid are not suitable purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) widely abundant in the human brain. As neuromodulators they play an important role functions such as attention, learning memory. Post-mortem studies reported lower expression α4β2-nAChRs more advanced...
Abstract Deposition of cross‐linked insoluble protein aggregates such as amyloid plaques is characteristic for Alzheimer's disease. Microglial activation by these extracullar deposits has been proposed to play a crucial role in functional degeneration well cell death neurones. A sugar‐derived post‐translational modification long‐lived proteins, advanced glycation endproducts (AGEs), activate specific signal transduction pathways, resulting the up‐regulation various pro‐inflammatory signals...
Summary β‐Amyloid (Aβ) plaques are characteristic hallmarks of Alzheimer's disease (AD). In AD, it has been suggested that activation microglial cells might be the link between Aβ deposition and neuronal degeneration. Activated microglia associated with senile produce free radicals inflammatory cytokines. However, is still not clear whether needs a prestimulated environment to exert its proinflammatory potential. Advanced glycation endproducts (AGEs), protein‐bound oxidation products sugars,...
Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R excellent inhibition of the monoamine oxidases cholinesterases, is an affine selective S1R agonist in nanomolar range, based on binding functional experiment, result confirmed by molecular modeling. In addition, contilisant significantly restores cognitive deficit induced Aβ1–42 radial maze assay vivo Alzheimer's disease test, comparing very favorably with donepezil.
Cannabinoid receptors type 2 (CB2) represent a target with increasing importance for neuroimaging due to its upregulation under various pathological conditions. Encouraged by preliminary results obtained [(11)C](Z)-N-(3-(2-methoxyethyl)-4,5-dimethylthiazol-2(3H)-ylidene)-2,2,3,3-tetramethyl-cyclopropanecarboxamide ([(11)C]A-836339, [(11)C]1) in mouse model of acute neuroinflammation (induced lipopolysaccharide, LPS), we designed library fluorinated analogues aiming an [(18)F]-labeled...
A series of various N-substituted 3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidines] (7) has been synthesized. In receptor binding studies, the N-benzyl derivative 7a (WMS-1813) revealed extraordinarily high sigma(1) affinity (K(i) = 1.4 nM) and excellent sigma(1)/sigma(2) selectivity (>600 fold). vitro biotransformation with rat liver microsomes led to three main metabolites. N-Debenzylation was inhibited by introduction an N-phenylethyl residue (7 g). The PET tracer [(18)F]7a...
Research Article31 May 2016Open Access Transparent process A novel thermoregulatory role for PDE10A in mouse and human adipocytes Mohammed K Hankir Integrated Treatment Centre Adiposity Diseases, University Hospital, of Leipzig, Germany Search more papers by this author Mathias Kranz Institute Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Neuroradiopharmaceuticals, Thorsten Gnad Pharmacology Toxicology, Bonn, Juliane Weiner Sally Wagner Winnie Deuther-Conrad...
The enantiomers of [(18)F]fluspidine, recently developed for imaging σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support translational potential, we estimated the human radiation dose (S)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]fluspidine from ex vivo biodistribution PET/MRI data mice after extrapolation to scale. In addition, validated preclinical results by performing a first-in-human PET/CT study using...
Glioblastoma (GBM) is still an incurable tumor that associated with high recurrence rate and poor survival despite the current treatment regimes. With urgent need for novel therapeutic strategies, immunotherapies, especially chimeric antigen receptor (CAR)-expressing T cells, represent a promising approach specific effective targeting of GBM. However, CAR cells can be serious side effects. To overcome such limitation, we applied our switchable RevCAR system to target both epidermal growth...
The cannabinoid receptor type 2 (CB2R) is overexpressed under pathological conditions. PET a suitable non‐invasive imaging technique for diagnosing disease states, but requires radiotracer that binds to CB2R with high affinity and selectivity. Currently, there no candidate routinely used in the clinics. naphthyridinone scaffold promising core structure has been modified past years. modification of carboxamides carboranes as hydrophobic surrogates purely organic moieties could lead beneficial...
Abstract Functional changes of nicotinic acetylcholine receptors (nAChR) are important during age‐related neuronal degeneration. Recent studies demonstrate the applicability nAChR ligand 2‐[ 18 F]F‐A‐85380 for neuroimaging patients with dementias. However, its binding kinetics demands a 7‐h acquisition time limiting practicality clinical PET studies. Thus, authors developed [ F]norchloro‐fluoro‐homoepibatidine ([ F]NCFHEB) imaging. The two enantiomers F]NCFHEB were compared F]F‐A85380 in...