Protein Composition of Multiple Sclerosis Myelin

Riekkinen, P.; Palo, J.; Arstila, Antti U.; Savolainen, H.; Rinne, U. K.; Kivalo, E; Frey, H.

doi:10.1001/archneur.1971.00480360079010

Cited by 39 publications

(10 citation statements)

References 25 publications

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“…The myelin fraction isolated from normal-appearing multiple sclerosis white matter contained normal amounts of basic and proteolipid pro¬ tein. Our finding confirms the earlier data of Enget al," as well as the most recent report of Wolfgram and Tourtellotte,13 but is at variance with the data of Riekkinen et al 12 The latter workers reported an almost total ab¬ sence of basic protein in myelin from normal-appearing multiple sclerosis white matter. We consider that the extremely low yield of their myelin isolation procedure is the most likely cause of this discrepancy.…”

Section: Commentsupporting

confidence: 93%

Myelin in Multiple Sclerosis

Suzuki¹

1973

Arch Neurol

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Myelin was isolated from white matter of five normal control brains and from normalappearing white matter of five patients with multiple sclerosis. There was statistically significant reduction of 25% to 30% in yield of myelin from abnormal brains, due probably to inadvertent inclusion of small lesions. No abnormalities were found in distribution of major constituents\p=m-\chloroform-methanol soluble and insoluble proteins and total lipid. Analysis of individual lipids, and fatty acid composition of sphin-golipids likewise did not show any differences between control and multiple sclerosis myelin. Contrary to a previous report, myelin isolated from normal-appearing white matter of multiple sclerosis brains contained normal amounts of myelin basic protein. Chemical composition of the myelin sheath in normal-appearing white matter of multiple sclerosis patients is, therefore, completely normal, at least for analytical factors examined.(28: [293][294][295][296][297] 1973) Multiple sclerosis appears to be primarily a disease of the mye¬ lin sheath. Chemical analyses of morphologically affected areas of the brain always show depletion of lipids, particularly of galactolipids, and the myelin basic protein. These findings reflect the decreased content of mye¬ lin in the affected areas. However, there are several reports in the litera¬ ture that describe decreased lipids and decreased polyunsaturated and long-chain fatty acids in histologically normal white matter of brains in multiple sclerosis patients.1"5 These findings led some investigators to a hypothesis that, in multiple sclerosis patients, there may be a primary abnormality in the lipid composition of the myelin sheath which predispos¬ es these individuals to multiple scle¬ rosis. However, the most recent study on the lipid composition of normalappearing white matter from six pa¬ tients showed only slight abnormali¬ ties, and these authors concluded that their findings could be explained by the presence of small lesions over-

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Section: Commentsupporting

confidence: 93%

Myelin in Multiple Sclerosis

Suzuki¹

1973

Arch Neurol

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“…However, it is now less evident that the glial cell membrane is the precursor of myelin. Not even traces of the encephalitogenic basic protein, the most integral and vulnerable part of myelin [ 13,14] could be demonstrated in glial cell membranes. Traces of encephalitogen were detected in neuronal membranes but only after a heavy loading.…”

Section: Discussionmentioning

confidence: 98%

Proteins of human glial cell membrane

Savolainen

Palo

1972

FEBS Letters

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“…This finding does not, however, rule out the possibility that the normal metabolism of myelin sheath is disturbed before any lysosomal changes are seen by electron microscopy [3,19,34], That this may be the case is suggested by chemical studies, which show that the different compo nents of myelin are affected at different stages of the disease [10,15,16,30], If myelin were degraded solely by the peeling-off process and subsequent 'bulk' digestion in the lysosomes, one would expect that dif ferent constituents would be lost approximately in the same proportion as they are present normal myelin. One possibility which must be taken into account in the degradation of myelin is the fact that purified myelin fractions both from CNS and from PNC contain proteinase activity as an integral of the membrane [1,18,21].…”

Section: Lysosomal Alterations and Their Relationship To Demyelinationmentioning

confidence: 94%

“…Most important in this respect have been those studies which indicate marked changes in the fatty acid com position of the white matter [5,7,16]. Recent histochemical and bio chemical studies have also revealed that the basic, encephalitogenic protein disappears from the myelin sheath early in the course of myelin break down [12,17,18,30], Although such studies strongly suggest that there are widely spread alterations in the myelin sheaths little is known at present on the extent of these alterations or on the mechanisms by which such alterations oc cur. In order to further study these questions the present investigation was undertaken.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Pathogenesis of Multiple Sclerosis

Riekkinen

et al. 1973

Eur Neurol

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The role of lysosomes in the pathogenesis of MS was studied by biochemical and ultrastructural techniques. Biochemical studies were performed on samples from 21 MS autopsies. The analyses included assays of acid proteinase, acid phosphatase, peptidase, neutral proteinase and esterase. The material for electron microscopy was obtained from ten biopsies made on MS patients during stereotaxic thalamotomy. In preliminary studies, the effect of autolysis on enzymatic activities was measured. These studies showed that acid hydrolases were stable enough to warrant further investigation. All enzyme activities studied were increased at the border zones of plaques, whereas in the macroscopically normal white matter only acid hydrolase activities were increased. Correspondingly, in electron microscopic studies, increased lysosomal response was found especially in astrocytes but also in oligodendrocytes. In astrocytes the number of heterolysosomes was conspicously increased and they were seen both in the perikaryon and in the cell processes. Such lysosomes often contained myelin-like membrane material. The presence of foreign phagocytizing cells could not be demonstrated except around the blood vessels. Furthermore, it appeared that myelin layers were not phagocytized by direct peeling process. These studies, suggest that early lysosomal changes occur in MS white matter and that such changes are mainly due to the phagocytosis of myelin inside astrocyte lysosomes. The possibility that the astrocyte response is a secondary phenomenon, which is preceded by other myelin destroying mechanisms is discussed.

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Protein Composition of Multiple Sclerosis Myelin

Cited by 39 publications

References 25 publications

Myelin in Multiple Sclerosis

Myelin in Multiple Sclerosis

Proteins of human glial cell membrane

Studies on the Pathogenesis of Multiple Sclerosis

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