A5005416332- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Insect and Pesticide Research
- Academic and Historical Perspectives in Psychology
- Social Representations and Identity
- Philosophy and History of Science
- Ion channel regulation and function
- Embodied and Extended Cognition
- Cholinesterase and Neurodegenerative Diseases
- Psychosomatic Disorders and Their Treatments
- Trace Elements in Health
- Political Philosophy and Ethics
- Science and Climate Studies
- Photoreceptor and optogenetics research
- Critical Theory and Philosophy
- Semiotics and Representation Studies
- Origins and Evolution of Life
- Lipid Membrane Structure and Behavior
- Biomedical Text Mining and Ontologies
- Action Observation and Synchronization
- Drug Transport and Resistance Mechanisms
- Philosophical Ethics and Theory
- Pharmacological Receptor Mechanisms and Effects
- Monoclonal and Polyclonal Antibodies Research
- Neural and Behavioral Psychology Studies
University of Copenhagen
2013-2021
ETH Zurich
2019
NeuroSearch (Denmark)
2013-2015
Saniona (Denmark)
2015
The University of Sydney
2014-2015
Despite extensive studies on nicotinic acetylcholine receptors (nAChRs) and homologues, details of binding are not completely resolved. Here, we report the crystal structure bound to receptor homologue protein from Lymnaea stagnalis. This is first in a pocket containing all five aromatic residues conserved mammalian nAChRs. The ligand-protein interactions characterized by contacts box formed primarily principal side intersubunit interface (residues Tyr89, Trp143 Tyr185). Besides these side,...
Positive allosteric modulators (PAMs) of α4β2 nicotinic acetylcholine receptors have the potential to improve cognitive function and alleviate pain. However, only a few selective PAMs been described limiting both pharmacological understanding drug-discovery efforts. Here, we describe novel PAM receptors, NS206, compare with previously reported PAM, NS9283. Using two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes, NS206 was observed positively modulate (ACh)-evoked...
Modulation of Cys loop receptor ion channels is a proven drug discovery strategy, but many underlying mechanisms the mode action are poorly understood. We report x-ray structure acetylcholine-binding protein from Lymnaea stagnalis with NS9283, stoichiometry selective positive modulator that targets α4-α4 interface α4β2 nicotinic acetylcholine receptors (nAChRs). Together homology modeling, mutational data, quantum mechanical calculations, and pharmacological studies on nAChRs, reveals...
Neuronal <i>α</i>4<i>β</i>2 nicotinic acetylcholine receptors are attractive drug targets for psychiatric and neurodegenerative disorders smoking cessation aids. Recently, a third agonist binding site between two <i>α</i>4 subunits in the (<i>α</i>4)<sub>3</sub>(<i>β</i>2)<sub>2</sub> receptor subpopulation was discovered. In particular, three residues, H142, Q150, T152, were demonstrated to be involved distinct pharmacology of <i>α</i>4-<i>α</i>4 versus <i>α</i>4-<i>β</i>2 sites. To obtain...