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The researchers of the IBCh RAS took part at the international conference nAChR 2017

From 7 to 11 May the fourth international conference on nicotinic acetylcholine receptors (nAChR 2017) was held on the island of Crete (Greece) in which scientists from the Institute of Bioorganic Chemistry RAS took part. Together with other leading experts in the field of neurobiology associated with cholinergic transmission, they discussed the genetic, molecular, structural and cellular aspects of research and told what key trends in the development of this scientific area are actively supported now.

nAChR

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The nAChR 2017 international conference was devoted to a discussion of current research on nicotinic receptors, creating opportunities for the design of new drugs with high selectivity and specificity for different subtypes of these receptors. The conference discussed a wide range of issues related to allosteric modulation, structural organization and regulation of the nicotinic acetylcholine receptors activity. Much attention was paid to intracellular delivery and assembly of functional receptors with the help of Nacho and RIC3 proteins, ​​as well as technical research issues. In addition, part of the conference reports touched on the achievements in the study of other pharmacologically important members of the Cys-receptor receptors superfamily, such as γ-aminobutyric acid and serotonin receptors.

The Institute of Bioorganic Chemistry of the Russian Academy of Sciences was represented by researchers from the Department of Molecular Bases of Neurosignalization (D.Sc., Corresponding Member of the Russian Academy of Sciences Victor Tsetlin, who was a member of the Program Committee, invited speaker and co-chairman at one of the sessions, D.Sc. Igor Kasheverov, D.Sc. Yury Utkin, Ph.D. Elena Kryukova and Ph.D. Irina Shelukhina) and the Bioengineering Department (Ph.D. Ekaterina Lyukmanova, Ph.D. Mikhail Shulepko, Ph.D. Natalia Vasilyeva and Dmitry Kulbatsky).

The researchers from the Bioengineering Department together with Nigel Unwin (in the center), British neuroscientists who obtained an atomic model of this ion channel, in its native membrane setting, in 2005.

“My group presented new data on the investigation of the secreted human proteins SLURP1 and SLURP2 anti-cancer activity and data on the human Lynx1 protein “protective” action on the long-term potentiation of the hippocampal neurons in the presence of beta-amyloid peptide,” says Ekaterina Lyukmanova. “For us, it was significant that the important role of Ly6/uPAR proteins in regulating the activity of nicotinic receptors, and this is exactly the direction my group is working on, has been repeatedly emphasized by the participants of the conference.”

The researchers of the IBCh RAS noted a number of tendencies that sounded at the conference during speeches and discussions.

“Several recent conferences on nicotinic acetylcholine receptors clearly demonstrate that an important role in our area is played by the stoichiometry of the receptor subunits. Their changes entails the appearance of new binding sites with different affinities and the degree of affinity is very important: in which area of ​​the brain or in what cells of the immune system are these receptors and what happens to them in a particular disease?” says Viktor Tsetlin. “Also recently, experts began focusing on steroids and the lipid environment in general on the acetylcholine receptor activity. In addition, the conference had many reports on the search for allosteric modulators. Nowadays it is not possible to find a selective α7 receptor agonist that could become a cure for Alzheimer's disease, therefore the researchers turned their attention to allosteric modulators. The experiments carried out on models, mainly involving acetylcholine-binding protein, which allow us hope for the creation of new compounds with higher affinity and selectivity. I am pleased to note that the α-conotoxins that we have been studied for a long time are the record holders. Also I was glad that the new high-affinity analogues of α-conotoxin PnIA, were proposed on the basis of a new computer program developed at Roman Efremov Laboratory of Biomolecular Modeling and were tested against the α7 neuronal receptor using radioligand analysis, fluorescence and electrophysiology, received a high mark.”

As a result, the researchers of the IBCh RAS presented five verbal and seven posters at the conference, which, as the researchers note, is a good indicator of their work recognition in the international community.

Earlier, the international conference on nicotinic acetylcholine receptors nAChR was conducted three times in Cambridge (Great Britain) - in 2008, 2011 and 2014.

The photo was provided by the organizers of the conference by the request of V. Tsetlin.

 

may 31, 2017