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INSTITUTE OF PHYSIOLOGY CAS

Cutting-edge science for health

Laboratory of Neurochemistry

Laboratory of Neurochemistry

We study the physiology, biochemistry and pharmacology of cholinergic neurons at molecular level. In our study we mainly employ cell lines but we also use animal models. Our research is focused mainly on these topics:

  • Biochemical physiology and pharmacology of cholinergic neurons. Development and differentiation of cholinergic neurons. Synthesis, storage, and release of acetylcholine. Presynaptic regulation of acetylcholine release.
  • Cholinergic mechanisms in pathogenesis of Alzheimer´s disease. Influence of beta-amyloid on acetylcholine metabolism and muscarinic transmission.
  • Molecular pharmacology of muscarinic receptors. Allosteric modulation of receptor activation. Interaction of muscarinic receptors with G-proteins. Modeling of muscarinic receptor signal transduction.

Projects

Cholinergic modulation of striatum-based behaviour

The aim of the project is to determine how disruption of cholinergic activation of striatal GABAergic interneurons alters striatal signalling and striatum-based behaviour by using a mouse model with deletion of the β2 nicotinic acetylcholine receptor subunit in striatal GABAergic interneurons. More

Achievements

Role of membrane cholesterol in differential sensitivity of muscarinic receptor subtypes to persistently bound xanomeline

Our new publication in journal Neuropharmacology in which we demonstrate that membrane cholesterol plays an important and subtype-specific role in activation of muscarinic acetylcholine receptors. To our knowledge, this is the first demonstration of pharmacological selectivity due to differences in receptor-membrane interactions at any GPCR. The possibility to achieve pharmacological selectivity based on receptor-membrane interactions changes our view on the molecular basis of pharmacological selectivity and opens new ways for the development of a novel pharmaceutics. More

Publications

Randáková; Alena - Nelic; Dominik - Ungerová; Dana - Nwokoye; P. - Su; Q. - Doležal; Vladimír - El-Fakahany; E. E. - Boulos; J. - Jakubík; Jan . Novel M-2-selective; G(i)-biased agonists of muscarinic acetylcholine receptors . British Journal of Pharmacology. 2020; 177(9); 2073-2089 . IF = 7.730 [ASEP] [ doi ]
Randáková; Alena - Nelic; Dominik - Doležal; Vladimír - El-Fakahany; E. E. - Boulos; J. - Jakubík; Jan . Agonist-Specific Conformations of the M-2 Muscarinic Acetylcholine Receptor Assessed by Molecular Dynamics . Journal of Chemical Information and Modeling. 2020; 60(4); 2325-2338 . IF = 4.549 [ASEP] [ doi ]
Jakubík; Jan - El-Fakahany; E. E. Current Advances in Allosteric Modulation of Muscarinic Receptors . Biomolecules. 2020; 10(2)); 325 . IF = 4.082 [ASEP] [ doi ]
Jakubík, Jan - Randáková, Alena - Rudajev, Vladimír - Zimčík, Pavel - El-Fakahany, E. E. - Doležal, Vladimír . Applications and limitations of fitting of the operational model to determine relative efficacies of agonists . Scientific Reports 2019, 9(Mar 15)), 4637 . IF = 3.998 [ASEP] [ doi ]
Jakubík, Jan - Randáková, Alena - El-Fakahany, E. E. - Doležal, Vladimír . Analysis of equilibrium binding of an orthosteric tracer and two allosteric modulators . PLoS ONE 2019, 14(3)), e0214255 . IF = 2.740 [ASEP] [ doi ]

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People

Mgr. Jan Jakubík, Ph.D.
Head of the Laboratory
MUDr. Vladimír Doležal, DrSc.
Deputy Head of the Laboratory
MUDr. et Mgr. Helena Janíčková, Ph.D.
Junior Scientist
Mgr. Alena Randáková, Ph.D.
Junior Scientist
  Mgr. Eva Dolejší, Ph.D.
Postdoctoral Fellow
Alice Abbondanza
Postgraduate Student
  Martina Hochmalová
Technician
Dana Ungerová
Technician
Dominik Nelic
Student
  Bc. Alexandra Tyshkevich
student
Jakub Danzig
Student
Trisha Dhabalia
Student
Jana Bláhová
Student