Axon

Axon- a single process of a nerve cell, reaching a length of up to 1.5 meters, of constant diameter, covered with neuroglial membranes. Axon conducts nerve impulses from the nerve cell body to other neurons or to working organs. At the point where the axon leaves the body, there is axon hillock, which, tapering, passes into the initial segment of the axon, not yet covered with a neuroglial sheath. The axon hillock lacks Nisl substance.

The cell membrane of an axon is called axolemma, and the cytoplasm is axoplasm. The axolemma plays a vital role in conducting nerve impulses. The axoplasm contains neurofibrils, mitochondria and agranular ER. All these organelles are greatly elongated. In the axoplasm there is a constant molecular current from the neuron body to the periphery and in the opposite direction.

The axon is divided into several large ones branches, which depart from the Ranvier interceptions. These branches end in numerous branches - terminals. They form synapses on other neurons.

The axon is always covered with a neuroglial sheath. Depending on the nature of the structure of the shells, they are distinguished 2 fiber types:

1) unmyelinated(pulpless);

2) myelinated(pulpy).

Unmyelinated fibers are mainly found in the autonomic nervous system and are small in diameter. Such an axon is immersed in a neuroglial cell so that the membrane of the neuroglial cell closes over the axon, enveloping it on all sides, forming mesaxon.

It has been established that up to 10-20 axons can penetrate into one neuroglial cell. Such fibers are called cable type fibers. In this case, the membrane is formed by a chain of neuroglial cells.

The second type of fibers is called unmyelinated. They have a larger axon diameter.

Neuroglial sheath consists of two layers: inner layer - myelin shell, outer layer - neurilemma.

The length of the myelin sheath begins slightly away from the axon body and ends at a distance of 2 µm from the synapse. It consists of segments of equal length - internodal segments, separated by interceptions of Ranvier. Here the axon is either exposed or covered by the neurilemma. Branches may arise in the area of ​​the nodes of Ranvier. The myelin sheath is an ordered structure that consists of alternating protein and lipid layers. Its structural unit is a bimolecular lipid layer sandwiched between two molecular protein layers. The thickness of this subunit is 115-130 A, and the number of layers themselves can reach 100 or more. The myelin sheath is insulator and has great resistance DC, which contributes to a huge acceleration of nerve impulse transmission. The nerve impulse seems to jump from one node of Ranvier to another, since depolarization of axons occurs only in the areas of nodes of Ranvier. This conduction of a nerve impulse is called sitetoric(spacing).

Oligodendrocytes and Schwann cells form myelin sheaths around axons (nerve cell processes). The myelin sheath helps nerves transmit signals. The myelin sheath of nerves consists of 70-75% lipids and 25-30% proteins. So, here are the remedies that will help support the restoration and regeneration of the myelin sheath, as well as prevent sclerosis.

1. Provide yourself with dietary supplements in the form of folic acid and vitamin B12. The body requires these two substances to protect the nervous system and properly repair myelin sheaths. 5. Eat foods high in choline (vitamin D) and inositol (inositol; B8). These amino acids are critical for the restoration of myelin sheaths.

6. Eat foods rich in B vitamins. Vitamin B-1, also called thiamine, and B-12 are physical components of the myelin sheath.

If it is damaged, memory problems arise, and a person often develops specific movements and functional impairments. Both folic acid and B12 can both help prevent the breakdown and regenerate damage to myelin. You can find choline in eggs, beef, beans and some nuts.

Anatomically, they include neuroglial cells in the brain (oligodendrocytes and astrocytes) and Schwann cells in the peripheral nervous system

Nuts, vegetables and bananas contain inositol. 7. You also need food containing copper. Lipids can only be created using copper-dependent enzymes. Copper is found in lentils, almonds, pumpkin seeds, sesame seeds and semi-sweet chocolate. Main functional elements nervous system are nerve cells or neurons, making up 10-15% total number cellular elements in the nervous system.

Glial elements, which make up the bulk of nervous tissue, perform auxiliary functions and fill almost all the space between neurons. The main functions of myelin: metabolic insulation and acceleration of nerve impulses, as well as support and barrier functions.

Nerve diseases associated with myelin destruction can be divided into two main groups - myelinopathies and myelinoclastics. Myelinoclastic diseases are based on the destruction of normally synthesized myelin under the influence of various influences, both external and internal.

The leukodystrophy group is characterized by demyelination with diffuse fibrous degeneration of the white matter of the brain and the formation of globoid cells in the brain tissue. Among myelinoclastic diseases, viral infections deserve special attention, in the pathogenesis of which myelin destruction plays an important role.

Treatment of all viral infections is based on the use of antiviral drugs that stop the virus from reproducing in infected cells. After chemotherapy and radiation therapy, toxic leukoencephalopathy with focal demyelination in combination with multifocal necrosis may develop. In the pathogenesis of these diseases, autoimmune reactions to myelin antigens, damage to oligodendrocytes and, consequently, disruption of remyelination processes are essential.

Consumption of products containing lecithin is a good prevention and one of the ways to treat diseases associated with disorders of the nervous system.

In this disease, large foci of demyelination form primarily in the white matter of the frontal lobes, sometimes involving the gray matter. The lesions consist of alternating areas of complete and partial demyelination with pronounced early defeat oligodendrocytes. Destruction of myelin and the development of autoimmune reactions to its components are observed in many vascular and paraneoplastic processes in the central nervous system (E.I. Gusev, A.N. Boyko.

The autoimmune process is accompanied by the appearance of myelinotoxic antibodies and killer T-lymphocytes that destroy Schwann cells and myelin. For correction immune system immunosuppressants are used, which reduce the activity of the immune system, and immunomodulators, which change the ratio of the components of the immune system.

If there are sources of chronic inflammation in the body or autoimmune diseases the integrity of the myelin sheaths of the nerves is impaired. Certain autoimmune diseases and external chemical factors, such as pesticides in food, can damage the myelin sheath. None of the sources known to the authors mention the property of stephaglabrine sulfate to restore the damaged myelin sheath of the nerve fiber.

The central nervous system (CNS) is a single mechanism that is responsible for the perception of the surrounding world and reflexes, as well as for controlling the system internal organs and fabrics. The last point is performed by the peripheral part of the central nervous system with the help of special cells called neurons. They make up the nervous tissue, which serves to transmit impulses.

The processes coming from the body of the neuron are surrounded by a protective layer that nourishes the nerve fibers and accelerates impulse transmission, and this protection is called the myelin sheath. Any signal transmitted along nerve fibers resembles a current discharge, and it is their outer layer that prevents its strength from decreasing.

If the myelin sheath is damaged, then full perception in this part of the body is lost, but the cell can survive and the damage will heal over time. If the injuries are quite serious, you will need drugs designed to restore nerve fibers like Milgamma, Copaxone and others. Otherwise, the nerve will die over time and perception will decrease. Diseases that are characterized by this problem include radiculopathy, polyneuropathy, etc., but doctors consider multiple sclerosis (MS) to be the most dangerous pathological process. Despite strange name, the disease has nothing to do with the direct definition of these words and when translated means “multiple scars.” They arise on the myelin sheath in the spinal cord and brain due to immune failure, which is why MS is classified as an autoimmune disease. Instead of nerve fibers, a scar consisting of connective tissue appears at the site of the lesion, through which the impulse can no longer pass correctly.

Is it possible to somehow restore damaged nerve tissue or will it forever remain in a crippled state is a relevant question to this day. Doctors still cannot answer this question accurately and have not yet come up with a full-fledged drug to restore sensitivity to nerve endings. Instead, there are various medications that can reduce the process of demyelination, improve nutrition of damaged areas and activate the regeneration of the myelin sheath.

Milgamma is a neuroprotector for restoring metabolism inside cells, which allows you to slow down the process of myelin destruction and begin its regeneration. The drug is based on vitamins from group B, namely:

  • Thiamine (B1). It is essential for the absorption of sugar in the body and the production of energy. With acute thiamine deficiency, a person's sleep is disturbed and memory deteriorates. He becomes nervous and sometimes depressed, as in depression. In some cases, symptoms of paresthesia are observed (goose bumps, decreased sensitivity and tingling in the fingertips);
  • Pyridoxine (B6). This vitamin plays an important role in the production of amino acids, as well as some hormones (dopamine, serotonin, etc.). Despite rare cases of a lack of pyridoxine in the body, due to its deficiency, a decrease in mental abilities and a weakening of the immune defense are possible;
  • Cyanocobalomin (B12). It serves to improve the conductivity of nerve fibers, resulting in improved sensitivity, as well as to improve blood synthesis. With a lack of cyanocobalamine, a person develops hallucinations, dementia (dementia), disturbances in heart rhythm and paresthesia are observed.

Thanks to this composition, Milgama is able to stop the oxidation of cells by free radicals (reactive substances), which will affect the restoration of sensitivity of tissues and nerve endings.

After a course of taking pills, there is a decrease in symptoms and an improvement in general condition, and the drug must be taken in 2 stages. In the first, you will need to make at least 10 injections, and then switch to tablets (Milgamma compositum) and take them 3 times a day for 1.5 months. Staphaglabrine sulfate has been used for quite a long time to restore the sensitivity of tissues and the nerve fibers themselves. The plant from whose roots this drug is extracted grows only in subtropical and tropical climates, for example, in Japan, India and Burma, and it is called smooth stephania. There are known cases of obtaining Stafaglabrine sulfate in laboratory conditions. Perhaps this is due to the fact that stephania smooth can be grown as a suspension culture, that is, in a suspended position in glass flasks with liquid. The drug itself is a sulfate salt, which has high temperature

Stephaglabrin sulfate serves to reduce the activity of enzymes from the class of hydrolases (cholinesterase) and to improve the tone of smooth muscles that are present in the walls of blood vessels, organs (hollow inside) and lymph nodes. It is also known that the drug is slightly toxic and can reduce blood pressure. In the old days, the medicine was used as an anticholinesterase agent, but then scientists came to the conclusion that Stefaglabrin sulfate is an inhibitor of connective tissue growth activity. From this it turns out that it delays its development and scars do not form on the nerve fibers. That is why the drug began to be actively used for injuries to the PNS.

During the research, specialists were able to see the growth of Schwann cells, which produce myelin in the peripheral nervous system. This phenomenon means that under the influence of the medication the patient noticeably improves the conduction of impulses along the axon, since the myelin sheath begins to form around it again. Since the results were obtained, the drug has become hope for many people diagnosed with incurable demyelinating pathologies.

It will not be possible to solve the problem of autoimmune pathology only by restoring nerve fibers. After all, no matter how many foci of damage have to be eliminated, the problem will return, since the immune system reacts to myelin as if it were foreign body and destroys it. Today it is impossible to eliminate such a pathological process, but you no longer have to wonder whether the nerve fibers are being restored or not. People are left to maintain their condition by suppressing the immune system and using drugs like Stefaglabrin sulfate to maintain their health.

The drug can only be used parenterally, that is, past the intestines, for example, by injection. The dosage should not exceed 7-8 ml of 0.25% solution per day for 2 injections. Judging by time, usually the myelin sheath and nerve endings are restored to some extent after 20 days, and then a break is needed and you can understand how long it will last by asking your doctor about it. The best result, according to doctors, can be achieved through low doses, since side effects develop much less frequently, and the effectiveness of treatment increases.

In laboratory conditions, during experiments on rats, it was found that with a concentration of the drug Stefaglabrin sulfate of 0.1-1 mg/kg, treatment proceeds faster than without it. The course of therapy ended in more than early dates, when compared to animals that did not take this medicine. After 2-3 months, the rodents’ nerve fibers were almost completely restored and the impulse was transmitted along the nerve without delay. In the experimental subjects who were treated without this medication, recovery lasted about six months and not all nerve endings returned to normal.

Copaxone

There is no cure for multiple sclerosis, but there are drugs that can reduce the effect of the immune system on the myelin sheath, and these include Copaxone. The essence of autoimmune diseases is that the immune system destroys the myelin located on nerve fibers. Because of this, the conductivity of impulses deteriorates, and Copaxone is able to change the target of the body’s defense system to itself. The nerve fibers remain untouched, but if the body’s cells have already begun to corrode the myelin sheath, then the drug will be able to push them aside. This phenomenon occurs because the drug is very similar in structure to myelin, so the immune system switches its attention to it.

The drug is capable of not only attacking the body’s defense system, but also producing special cells of the immune system to reduce the intensity of the disease, called Th2 lymphocytes. The mechanism of their influence and formation has not yet been thoroughly studied, but there are various theories. There is an opinion among experts that dendritic cells of the epidermis are involved in the synthesis of Th2 lymphocytes.

The produced suppressor (mutated) lymphocytes, entering the blood, quickly penetrate into the part of the nervous system where the source of inflammation is located. Here, Th2 lymphocytes, due to the influence of myelin, produce cytokines, that is, anti-inflammatory molecules. They begin to gradually relieve inflammation in this area of ​​the brain, thereby improving the sensitivity of nerve endings.

The drug has benefits not only for the treatment of the disease itself, but also for the nerve cells themselves, since Copaxone is a neuroprotector. The protective effect is manifested in stimulating the growth of brain cells and improving lipid metabolism. The myelin sheath mainly consists of lipids, and in many pathological processes associated with damage to nerve fibers, they are oxidized, so the myelin is damaged. The drug Copaxone can eliminate this problem, as it increases the body's natural antioxidant (uric acid). It is not known why the level of uric acid increases, but this fact has been proven in numerous experiments.

The drug serves to protect nerve cells and reduce the severity and frequency of exacerbations. It can be combined with medications Stefaglabrin sulfate and Milgamma.

The myelin sheath will begin to recover due to the increased growth of Schwann cells, and Milgamma will improve intracellular metabolism and enhance the effect of both drugs. Using them yourself or changing the dosage yourself is strictly prohibited.

Whether it is possible to restore nerve cells and how long it will take only a specialist can answer, based on the results of the examination. It is prohibited to take any medications on your own to improve tissue sensitivity, since most of them are hormonal and therefore difficult to tolerate by the body.

Component

In myelin

In white matter

In gray matter

Squirrels

Total phospholipids

Fophatidylserine

Phosphatidylinositol

Cholesterol

Sphingomyelin

Cerebosides

Plasmogens

gangliosides

The structure of the nerve fiber. Myelin sheath

The axons of neurons form nerve fibers. Each fiber consists of an axial cylinder (axon), inside of which there is axoplasm with neurofibrils, mitochondria and synaptic vesicles.

Depending on the structure of the sheaths enveloping the axons, nerve fibers are divided into: unmyelinated (pulpless) And myelin (pulp).

1. Unmyelinated fiber

Unmyelinated fiber consists of 7-12 thin axons that pass inside a cord formed by a chain of neuroglial cells.

Unmyelinated fibers have postganglionic nerve fibers that are part of the autonomic nervous system.

2. Myelin fiber

Myelin fiber consists of a single axon, which is enveloped myelin sheath and is surrounded by glial cells.

Myelin sheath formed by the plasma membrane of a Schwann or oligodendroglial cell, which is folded in half and wrapped repeatedly around the axon. Along the length of the axon, the myelin sheath forms short sheaths - internodes, between which there are unmyelized areas - Ranvier interceptions.

Myelinated fiber is more perfect than non-myelinated fiber, because it has a higher speed of nerve impulse transmission.

Myelin fibers have the conduction system of the somatic nervous system, preganglionic fibers of the autonomic nervous system.

Molecular organization of the myelin sheath (according to H. Hiden)

1-axon; 2-myelin; 3-axis fiber; 4-protein (outer layers); 5-lipids; 6-protein (inner layer); 7-cholesterol; 8-cerebroside; 9- sphingomyelin; 10-phosphatidylserine.

Chemical composition of myelin

Myelin contains a lot of lipids and little cytoplasm and proteins. On a dry weight basis, the myelin sheath membrane contains 70% lipids (which in total constitutes about 65% of all lipids in the brain) and 30% proteins. 90% of all myelin lipids are cholesterol, phospholipids and cerebrosides. Myelin contains some gangliosides.

The protein composition of myelin in the peripheral and central nervous systems is different. CNS myelin contains three proteins:

    Proteolipid, makes up 35–50% of the total protein content in myelin, has a molecular weight of 25 kDa, soluble in organic solvents;

    Basic protein A 1 , makes up 30% of the total protein content in myelin, has a molecular weight of 18 kDa, soluble in weak acids;

    Wolfgram proteins - several acidic proteins of large mass, soluble in organic solvents, the function of which is unknown. They make up 20% of the total protein content in myelin.

In PNS myelin, proteolipid is absent, the main protein is present proteins A 1 (A little), R 0 And R 2 .

Enzymatic activity has been detected in myelin:

    cholesterol esterase;

    phosphodiesterase, which hydrolyzes cAMP;

    protein kinase A, which phosphorylates the main protein;

    sphingomyelinase;

    carbonic anhydrase.

Due to its structure, myelin has higher stability (resistance to degradation) than other plasma membranes.

METABOLISM AND ENERGY IN NERVOUS TISSUE

Energy metabolism of nervous tissue

The brain is characterized by a high intensity of energy metabolism with a predominance of aerobic processes. Weighing 1400g (2% of body weight), it receives about 20% of the blood ejected by the heart and approximately 30% of the total oxygen in the arterial blood.

Maximum energy metabolism in the brain is observed during the period of completion of myelination and completion of differentiation processes in children aged 4 years. At the same time, rapidly growing nervous tissue consumes about 50% of all oxygen entering the body.

The maximum breathing rate was found in the cerebral cortex, the minimum - in the spinal cord and peripheral nerves. Neurons are characterized by aerobic metabolism, while the metabolism of neuroglia is also adapted to anaerobic conditions. The respiration rate of gray matter is 4 times higher than that of white matter.

Unlike other organs, the brain has virtually no oxygen reserves. The brain's reserve oxygen is consumed within 10-12 seconds, which explains the high sensitivity of the nervous system to hypoxia.

The main energy substrate of nervous tissue is glucose, the oxidation of which is provided by its energy by 85-90%. Nervous tissue consumes up to 70% of free glucose released from the liver into the arterial blood. Under physiological conditions, 85-90% of glucose is metabolized aerobically, and 10-15% anaerobically.

Neurons and glial cells can use as additional energy substrates amino acids , primarily glutamate and aspartate.

In extreme conditions, nervous tissue switches to ketone bodies(up to 50% of total energy).

In the early postnatal period, the brain also oxidizes free fatty acid and ketone bodies .

The resulting energy is spent first:

    to create membrane potential , which is used to conduct nerve impulses and active transport;

    for the functioning of the cytoskeleton , providing axonal transport, release of neurotransmitters, spatial orientation of the structural units of the neuron;

    for the synthesis of new substances , primarily neurotransmitters, neuropeptides, as well as nucleic acids, proteins, lipids;

    for ammonia neutralization .

Metabolism of carbohydrates in nervous tissue

Nervous tissue is characterized by high carbohydrate metabolism, in which glucose catabolism predominates. Since nerve tissue insulin-independent , with high activity hexokinase (has a low Michaelis Menton constant) and low glucose concentration, glucose flows from the blood into the nervous tissue constantly, even if there is little glucose in the blood and no insulin.

The activity of PFS in nervous tissue is low. NADPH 2 is used in the synthesis of neurotransmitters, amino acids, lipids, glycolipids, nucleic acid components and for the functioning of the antioxidant system.

High activity of PFS is observed in children during the period of myelination and with brain injuries.

Metabolism of proteins and amino acids in nervous tissue

Nervous tissue is characterized by a high metabolism of amino acids and proteins.

The rate of protein synthesis and breakdown in different parts of the brain is not the same. The proteins of the gray matter of the cerebral hemispheres and the proteins of the cerebellum are characterized by a high rate of renewal, which is associated with the synthesis of mediators, biologically active substances, and specific proteins. White matter, rich in conductive structures, is renewed especially slowly.

Amino acids in nerve tissue are used as:

    source of "raw materials" for the synthesis of proteins, peptides, some lipids, a number of hormones, vitamins, biogenic amines, etc. The synthesis of biologically active substances predominates in the gray matter, and the myelin sheath proteins predominate in the white matter.

    neurotransmitters and neuromodulators. Amino acids and their derivatives are involved in synaptic transmission (glu), in the implementation of interneuronal connections .

    Energy source .

    Nervous tissue oxidizes amino acids of the glutamine group and amino acids with a branched side chain (leucine, isoleucine, valine) into the TCA cycle. . To remove nitrogen

When the nervous system is excited, the formation of ammonia increases (primarily due to the deamination of AMP), which binds to glutamic acid to form glutamine. The ATP-consuming reaction is catalyzed by glutamine synthetase.

Amino acids of the glutamine group have the most active metabolism in nervous tissue. N

-acetylaspartic acid (AcA) is part of the intracellular pool of anions and a reservoir of acetyl groups. The acetyl groups of exogenous AcA serve as a carbon source for fatty acid synthesis in the developing brain.

Aromatic amino acids are of particular importance as precursors of catecholamines and serotonin.

Methionine is a source of methyl groups and is 80% used for protein synthesis.

Cystathionine

important for the synthesis of sulfitides and sulfatilated mucopolysaccharides.

Nitrogen exchange in nervous tissue

The direct source of ammonia in the brain is indirect deamination of amino acids with the participation of glutamate dehydrogenase, as well as deamination with the participation of the AMP-IMP cycle.

The neutralization of toxic ammonia in nervous tissue occurs with the participation of α-ketoglutarate and glutamate.

Lipid metabolism of nervous tissue

A peculiarity of lipid metabolism in the brain is that they are not used as energy material, but are mainly used for construction needs. Lipid metabolism is generally low and differs in white and gray matter.

In neurons of the gray matter, phosphotidylcholines and especially phosphotidylinositol, which is a precursor of the intracellular messenger ITP, are most intensively renewed from phosphoglycerides.

Cerebroside is the most typical component of myelin. With the exception of the very early period of development of the organism, the concentration of cerebroside in the brain is directly proportional to the amount of myelin in it. Only 1/5 of the total galactolipid content in myelin occurs in sulfated form. Cerebrosides and sulfatides play an important role in ensuring myelin stability.

Myelin is also characterized high level its main lipids are cholesterol, total galactolipids and ethanolamine-containing plasmalogen. It has been established that up to 70% of brain cholesterol is found in myelin. Since nearly half of the brain's white matter can be composed of myelin, it is clear that the brain contains the highest amount of cholesterol compared to other organs. The high concentration of cholesterol in the brain, especially in myelin, is determined by the main function of neuronal tissue - to generate and conduct nerve impulses. The high cholesterol content in myelin and the uniqueness of its structure lead to a decrease in ionic leakage through the neuron membrane (due to its high resistance).

Phosphatidylcholine is also essential integral part myelin, although sphingomyelin is contained in relatively small amounts.

The lipid composition of both gray matter and white matter of the brain is distinctly different from that of myelin. The composition of myelin in the brain of all mammalian species studied is almost the same; only minor differences occur (eg, rat myelin has less sphingomyelin than bovine or human myelin). There is some variation and depending on the location of the myelin, for example myelin isolated from the spinal cord has a higher lipid to protein ratio than myelin from the brain.

Myelin also contains polyphosphatidylinositols, of which triphosphoinositide makes up 4 to 6% of the total myelin phosphorus, and diphosphoinositide makes up 1 to 1.5%. Minor components of myelin include at least three cerebroside esters and two glycerol-based lipids; Myelin also contains some long-chain alkanes. Mammalian myelin contains from 0.1 to 0.3% gangliosides. Myelin contains more monosialoganglioside bM1 compared to what is found in brain membranes. Myelin of many organisms, including humans, contains a unique ganglioside sialosylgalactosylceramide OM4.

PNS myelin lipids

The myelin lipids of the peripheral and central nervous systems are qualitatively similar, but there are quantitative differences between them. PNS myelin contains less cerebrosides and sulfatides and significantly more sphingomyelin than CNS myelin. It is interesting to note the presence of ganglioside OMP, which is characteristic of PNS myelin in some organisms. Differences in the composition of myelin lipids in the central and peripheral nervous systems are not as significant as their differences in protein composition.

CNS myelin proteins

The protein composition of CNS myelin is simpler than other brain membranes, and is represented mainly by proteolipids and basic proteins, which make up 60-80% of the total. Glycoproteins are present in much smaller quantities. Myelin of the central nervous system contains unique proteins.

Myelin of the human central nervous system is characterized by a quantitative predominance of two proteins: the positively charged cationic myelin protein (myelin basic protein, MBP) and myelin proteolipid protein, PLP. These proteins are the main components of the myelin of the central nervous system of all mammals.

Myelin proteolipid PLP (proteolipid protein), also known as Folch protein, has the ability to dissolve in organic solvents. The molecular weight of PLP is approximately 30 kDa (Da - Dalton). Its amino acid sequence is extremely conserved, and the molecule forms several domains. The PLP molecule contains three fatty acids, typically palmitic, oleic and stearic, linked to amino acid radicals by an ester bond.

CNS myelin contains slightly smaller amounts of another proteolipid, DM-20, named for its molecular weight (20 kDa). Both DNA analysis and primary structure elucidation showed that DM-20 is formed by the cleavage of 35 amino acid residues from the PLP protein. During development, DM-20 appears earlier than PLP (in some cases even before the appearance of myelin); suggest that in addition to its structural role in myelin formation, it may be involved in oligodendrocyte differentiation.

Contrary to the idea that PLP is required for the formation of compact multilamellar myelin, the process of myelin formation in PLP/DM-20 knockout mice occurs with only minor abnormalities. However, these mice have a reduced lifespan and impaired general mobility. In contrast, naturally occurring mutations in PLP, including normal PLP over-expression, have serious functional consequences. It should be noted that significant amounts of PLP and DM-20 proteins are present in the CNS; messenger RNA for PLP is present both in the PNS and not a large number of The protein is synthesized there, but is not included in myelin.

Cationic myelin protein (MCP) attracts the attention of researchers due to its antigenic nature - when administered to animals, it causes an autoimmune reaction, the so-called experimental allergic encephalomyelitis, which is a model of a severe neurodegenerative disease - multiple sclerosis.

The amino acid sequence of MBP is highly conserved in many organisms. MBP is located on the cytoplasmic side of myelin membranes. It has a molecular weight of 18.5 kDa and lacks signs of tertiary structure. This core protein exhibits microheterogeneity when electrophoresed under alkaline conditions. Most mammals studied contained varying amounts of MBR isoforms that shared a significant portion of their amino acid sequence. The molecular weight of MBR in mice and rats is 14 kDa. Low molecular weight MBR has the same amino acid sequences on the N- and C-terminal parts of the molecule as the rest of the MBR, but differs in the reduction of about 40 amino acid residues. The ratio of these major proteins changes during development: mature rats and mice have more 14-kDa MBRs than 18-kDa MBRs. The other two isoforms of MBR, also found in many organisms, have molecular masses of 21.5 and 17 kDa, respectively. They are formed by attaching a polypeptide sequence weighing about 3 kDa to the main structure.

Electrophoretic separation of myelin proteins reveals proteins with a higher molecular weight. Their number depends on the type of organism. For example, mice and rats can contain up to 30% of the total amount of such proteins. The content of these proteins also changes depending on the age of the animal: the younger it is, the less myelin there is in its brain, but the more proteins with a higher molecular weight it contains.

The enzyme 2"3"-cyclic nucleotide 3"-phosphodiesterase (CNP) makes up several percent of the total content of myelin protein in CNS cells. This is much more than in other types of cells. CNP protein is not the main component of compact myelin; it is concentrated only in certain areas of the myelin sheath associated with the cytoplasm of the oligodendrocyte. The protein is localized in the cytoplasm, but part of it is associated with the cytoskeleton of the membrane - F-actin and tubulin. The biological function of CNP may be to regulate the structure of the cytoskeleton to accelerate the processes of growth and differentiation in oligodendrocytes.

Myelin-associated glycoprotein (MAG) is a quantitatively minor component of purified myelin, has a molecular weight of 100 kDa, and is found in the CNS in small quantities (less than 1% of the total protein). MAG has a single transmembrane domain that separates the highly glycosylated extracellular portion of the molecule, composed of five immunoglobulin-like domains, from the intracellular domain. Its overall structure is similar to neuronal cell adhesion protein (NCAM).

MAG is not present in compact, multilamellar myelin, but is found in the periaxonal membranes of oligodendrocytes that form the myelin layers. Let us recall that the periaxonal membrane of the oligodendrocyte is closest to the plasma membrane of the axon, but nevertheless these two membranes do not merge, but are separated by an extracellular cleft. This feature of MAG localization, as well as the fact that this protein belongs to the immunoglobulin superfamily, confirms its participation in the processes of adhesion and information transfer (signaling) between the axolemma and myelin-forming oligodendrocytes during the process of myelination. In addition, MAG is one of the components of the white matter of the central nervous system that inhibits neurite growth in tissue culture.

Among other glycoproteins of white matter and myelin, the minor myelin-oligodendrocytic glycoprotein (MOG) should be noted. MOG is a transmembrane protein containing a single immunoglobulin-like domain. Unlike MAG, which is located in the inner layers of myelin, MOG is localized in its surface layers, which is why it can participate in the transmission of extracellular information to the oligodendrocyte.

Small amounts of characteristic membrane proteins can be identified by polyacrylamide gel electrophoresis (PAGE) (eg, tubulin). High resolution electrophoresis demonstrates the presence of other minor protein bands; they may be associated with the presence of a number of myelin sheath enzymes.

PNS myelin proteins

PNS myelin contains both some unique proteins and several common proteins with CNS myelin proteins.

P0 is the main protein of PNS myelin, has a molecular weight of 30 kDa, and makes up more than half of the PNS myelin proteins. It is interesting to note that although it differs from PLP in amino acid sequence, post-translational modification pathways and structure, both of these proteins are equally important for the formation of the structure of CNS and PNS myelin.

The MBP content in PNS myelin is 5-18% of the total protein, in contrast to the CNS, where its share reaches a third of the total protein. The same four forms of MBP protein with molecular masses of 21, 18.5, 17 and 14 kDa, respectively, found in CNS myelin are also present in the PNS. In adult rodents, MBP with a molecular weight of 14 kDa (named “Pr” according to the classification of peripheral myelin proteins) is the most significant component of all cationic proteins. PNS myelin also contains MBP with a molecular weight of 18 kDa (in this case it is called “P1 protein”). It should be noted that the importance of the MBP family of proteins is not as great for the myelin structure of the PNS as for the CNS.

PNS myelin glycoproteins

PNS compact myelin contains a 22-kDa glycoprotein called peripheral myelin protein 22 (PMP-22), which accounts for less than 5% of the total protein content. PMP-22 has four transmembrane domains and one glycosylation domain. This protein does not play a significant structural role. However, abnormalities of the pmp-22 gene are responsible for some hereditary human neuropathologies.

Several decades ago, it was believed that myelin creates an inert sheath that does not perform any biochemical functions. However, later a large number of enzymes were discovered in myelin that are involved in the synthesis and metabolism of myelin components. A number of enzymes present in myelin are involved in the metabolism of phosphoinositides: phosphatidylinositol kinase, diphosphatidylinositol kinase, corresponding phosphatases and diglyceride kinases. These enzymes are of interest due to the high concentration of polyphosphoinositides and their quick exchange. There is evidence of the presence of muscarinic cholinergic receptors, G-proteins, phospholipases C and E, and protein kinase C in myelin.

Na/K-ATPase, which carries out the transport of monovalent cations, as well as 6"-nucleotidase, was found in the myelin of the PNS. The presence of these enzymes suggests that myelin can take an active part in axonal transport.