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Information × Registration Number 0215U003384, 0110U005969 , R & D reports Title Study of regulatory mechanisms of nicotinic acetylcholine receptor -specific antibodies in immune cells. popup.stage_title Head Skok Maryna Volodymyrivna, Доктор біологічних наук Registration Date 28-01-2015 Organization A.V.Palladin Institute of Biochemistry of National Academy of Sciences popup.description2 In the course of the project, the nicotinic acetylcholine receptor (nAChR) subtypes expressed in the cells of monocyte (U937), astrocyte (U373) or В-lymphocyte origin (Daudi) have been analyzed. It was found that mitochondria are one of the intracellular compartments containing alpha7 nAChRs. Antibodies elicited against extracellular domain (1-208) nAChR increased the number of intracellular adhesion molecules ІСАМ-1 on the surface of Daudi cells and stimulated the production of pro-inflammatory interleukin-6 by U937 and U373 cells. The mechanism of the antibody effect was not related to the blockade of corresponding receptors or to pro-inflammatory properties of the Fc-fragment. The antibody binding itself generated intracellular signaling mediated by p38 kinase. Intravenous injections of alpha7(1-208)-specific antibodies in mice decreased alpha7 nAChR protein and mRNA expression in the brain and diminished the brain mitochondria resistance to the effect of Ca2+. Produced in vivo, alpha7 nAChR-specific antibodies stimulated interleukin-6 production and astrocytosis, decreased alpha7 nAChR level and favoured accumulation of pathological amyloid-betta in the brain and brain mitochondria of mice. The strongest changes have been observed in the hippocampus and were accompanied by the worsening of episodic memory of experimental animals. The data obtained indicate that inflammation induced by the alpha7 nAChR-specific antibodies stimulated the Alzheimer disease-like symptoms in mice. Correspondingly, the presence of alpha7 nAChR-specific antibodies in the human blood, combined with the conditions facilitating the antibody penetration into the brain, can be regarded as risk factors for the development of Alzheimer disease. Product Description popup.authors Гергалова Галина Леонідівна Калашник Олена Миколаївна Коваль Людмила Миколаївна Лихмус Олена Юріївна popup.nrat_date 2020-04-02 Close