Myelin cholesterol

Myelin Cholesterol Ccrcbrosidcs Phosphalidy leihanol amine Phosphatidylcholine 80% 20%... 

Fig. 3. Localization of chole.sterol in myelin. Cholesterol in the myelin sheath and endoneurial fat in rat seiatic nerve ( X 465) is stained by the perehlorie acid-naphthoquinone method (Adams, 1961). (By courtesy of Dr. C. W. M. Adams.)...

Component of the myelin sheath surrounding the axons of nerve cells. Additional compounds of the myelin sheath are phospholipids, cholesterol, cerebrosides, and specific keratins. The myelin sheath constitutes an isolating barrier during electrophysiological axonal signaling. 

The liquid crystalline state may be identified as a distinct and unique state of matter which is characterised by properties which resemble those of both solids and liquids. It was first recognised in the middle of the last century through the study of nerve myelin and derivatives of cholesterol. The research in the area really gathered momentum, however, when as a result of the pioneering work of Gray in the early 1970 s organic compounds exhibiting liquid crystalline properties were shown to be suitable to form the basis of display devices in the electronic products. 

Cholesterol is found in many biological membrane and is the main sterol of animal organisms. It is eqnimolar with phospholipids in membranes of liver cell, erythrocytes, and myelin, whereas in human stratum comeum it lies in the outermost layer of the epidermis... 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

Myelin components exhibit great heterogeneity of metabolic turnover. One of the novel characteristics of myelin demonstrated in early biochemical studies was that its overall rate of metabolic turnover is substantially slower than that of other neural membranes [1]. A standard type of experiment was to evaluate lipid or protein turnover by injecting rat brains with a radioactive metabolic precursor and then follow loss of radioactivity from individual components as a function of time. Structural lipid components of myelin, notably cholesterol, cerebro-side and sulfatide, as well as proteins of compact myelin, are relatively stable, with half-lives of the order of many months. One complication in interpreting these studies is that the metabolic turnover of individual myelin components is multiphasic - consisting of an initial rapid loss of radioactivity followed by a much longer slower loss. 

Another pathway of some importance occurs in the brain this is the cholesterol 24-hydroxylase pathway. About 25% of the body s cholesterol exists in the plasma membranes of myelin sheaths. Here, the blood-brain barrier prevents cholesterol exchanges with the circulating lipoproteins, which makes it difficult for cholesterol to leave the brain. The cytochrome P-450 enzymes (CYP 46), expressed almost exclusively in the endoplasmic reticula of the brain, allows formation of 24-hydroxycholesterol. 

Organotellurium compounds such as dimethyltellurium dichloride and dimethyltelluride have been reported as potential inhibitors of squalene monooxygenase, causing a dramatic reduction in the rate of cholesterol biosynthesis and leading to degradation of the myelin sheath. 

Human myelin sheath 30 30 19 Cholesterol Galactolipids, plasmalogens... 

The concept of ion-dipole interaction between lecithin and cholesterol has been suggested by many workers for the packing of these lipids in myelin or in the cell membrane (18, 19, 52). This concept is not supported by the surface potential measurements of mixed monolayers of lecithin and cholesterol. In contrast to dicetyl phosphate-cholesterol... 

Cholesterol makes up 17% of myelin and is present in plasma membranes. However, it usually does not occur in bacteria and is present only in trace amounts in mitochondria. Related sterols are present in plant membranes. Esters of sterols occur as transport forms but are not found in membranes. Membrane bilayers, likewise, contain little or no triacylglycerols, the latter being found largely as droplets in the cytoplasm. 

On the other hand, as we have already seen, cholesterol tends to reduce the mobility of molecules in membranes and causes phospholipid molecules to occupy a smaller area than they would otherwise. Myelin is especially rich in long-chain sphingolipids and cholesterol, both of which tend to stabilize artificial bilayers. Within our bodies, the bilayers of myelin tend to be almost solid. Bilayers of some gram-positive bacteria growing at elevated temperatures are stiffened by biosynthesis of bifunctional fatty acids with covalently joined "tails" that link the opposite sides of a bilayer.149... 

Genes coding for APO-E are associated with different risks for Alzheimer s disease. There are three alleles (or copies) of the gene coding for this apolipoprotein which are called E2, E3, and E4. For example, a gene on chromosome 19 that codes for APO-E is linked to many cases of late-onset Alzheimer s disease. Moreover, APO-E is associated with cholesterol transport and involved with other neuronal functions, including repair, growth, and maintenance of myelin sheaths and cell membranes. 

Toxicants may selectively target glial cells for a number of reasons. Myelinating glial cells constantly synthesize cholesterol and cerebroside for myelin production thus toxicants that affect these synthetic pathways will preferentially affect myelination. The hydrophobic nature of myelin may serve as a reservoir for lipophilic toxicants... 

In addition to the effect of increased VLCFA on membrane and possibly cellular function, the rapid cerebral form of X-ALD is characterized by an inflammatory response that is believed to contribute to the demyelination that characterizes this phenotype and which is similar to that seen in multiple sclerosis. These cerebral lesions are characterized by breakdown in myelin with sparing of the axons accompanied by the accumulation of cholesterol ester in the neurons. A perivascular inflammatory response with infiltration of T cells, B cells, and macrophages also is present. Therefore, it is believed that the rapid cerebral disease has an im-munologically-mediated component. It has been suggested that the inflammatory response occurs in response to the elevated levels of VLCFA in lipids, which elicits an inflammatory cascade that may be mediated in part by cytokines. Once this cascade begins, it may be more difficult to intervene in the disease process, and in general therapeutic interventions studied to date have been most effective when initiated early. Therefore, prevention of the initiation of the immune response is important for improving outcome. 

Myelin is modified plasma membrane. Myelin of the PNS resembles that of the CNS with respect to lipid composition. There is an enrichment in such specialized lipids as cerebroside and ethanolamine plasmalogen, and the high content of cholesterol plays an important role in control of membrane fluidity. The protein composition of PNS myelin is, however, distinct from that of CNS myelin. A single protein, P0, accounts for half of all protein of PNS myelin. Of the other proteins present, most are expressed in the CNS as well as the PNS but in quantitatively different amounts. Prominent among these proteins are myelin basic proteins and myelin-associated glycoprotein. 

Enzymes. Many enzyme activities have been found in myelin neuraminidase, cholesterol ester hydrolase, lipid synthesizing and catabolizing enzymes, proteases, protein kinases, and phosphatases. Two of them have been especially characterized. 

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