Molecular mechanisms of molecular transfer across the blood-brain barrier as a target for pharmacological action. Part 1. Structure, function and pathology of the BBB

Alexander N. Trofimov; Mariya V. Litvinova; Alexander P. Schwarz; Vera V. Kosheverova; Andrei A. Lebedev; Nikolai A. Arseniev; Alexander I. Tyukavin

doi:10.17816/phf109914

Pharmacy Formulas ›› 2022, Vol. 4 ›› Issue (2) :60 -69. DOI: 10.17816/phf109914

Actual problems: discussion tribune

review-article

Molecular mechanisms of molecular transfer across the blood-brain barrier as a target for pharmacological action. Part 1. Structure, function and pathology of the BBB

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Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation

Institute of Experimental Medicine

I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Institute of Cytology of the Russian Academy of Sciences

Saint Petersburg Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation

Ph.D. in Biological Sciences, Senior Researcher at the I.P. Pavlov Department of Physiology, Associate Professor at the Department of Physiology and Pathology

Postgraduate Student at the S. V. Anichkov Department of Neuropharmacology; Laboratory Assistant at the Department of Physiology and Pathology

Ph.D. in Biological Sciences, Researcher at the Laboratory of Molecular Mechanisms of Neural Interactions

Ph.D. in Biological Sciences, Researcher at the Laboratory of Intracellular Membrane Dynamics

Doctor of Biological Sciences, Professor, Head of the Laboratory of General Pharmacology, S. V. Anichkov Department of Neuropharmacology

Ph.D. in Biological Sciences, Associate Professor at the Department of Physiology and Pathology

Doctor of Medical Sciences, Professor, Head of the Department of Physiology and Pathology

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Abstract

Biological barriers play a key role in maintaining the integrity and functioning of the body at all levels of its organization. The barrier function at the cellular level is based on the hydrophobic properties of the cytoplasmic membrane, which provide selective permeability for various substances, depending on their chemical properties. At higher levels of organization, from tissue to organism, the barrier function is based on intercellular protein complexes of the plasma membrane, which form paracellular diffusion barriers and separate internal and external fluid media, which is a necessary condition for the development and functioning of each organ. The blood-brain barrier (BBB) plays an important role in maintaining the function of the brain. The review reflects the main stages in the embryonic development of the BBB, as well as presents current data on the morphological and functional features of the organization of the BBB, including molecular mechanisms that mediate the barrier function due to the complex participation of vascular cells of cerebral microvessels, as well as gene expression of enzyme complexes, active and passive substance transport mechanisms through the BBB. The high transport selectivity of the BBB is an urgent problem for the delivery of drugs to the brain. At the same time, it is equally important to improve the principles of pharmacotherapy for the correction of impaired BBB functions in various types of pathology of the nervous and other body systems. This review aims to convey to the developers of modern targeted drugs new information about the molecular genetic mechanisms of the transport of substances through the BBB, as well as to draw the attention of specialists in the field of precision medicine to the problem of violations of the barrier function of cerebral vessels in neurological and other diseases of a modern person.

Keywords

blood-brain barrier / mechanisms of mass transfer across the BBB / central nervous system / pharmacotherapy / precision medicine / platelet-derived growth factor

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Alexander N. Trofimov, Mariya V. Litvinova, Alexander P. Schwarz, Vera V. Kosheverova, Andrei A. Lebedev, Nikolai A. Arseniev, Alexander I. Tyukavin. Molecular mechanisms of molecular transfer across the blood-brain barrier as a target for pharmacological action. Part 1. Structure, function and pathology of the BBB. Pharmacy Formulas, 2022, 4(2): 60-69 DOI:10.17816/phf109914

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