Molecular Architecture of Myelin

Braun, Peter E.

doi:10.1007/978-1-4615-7514-6_3

Cited by 39 publications

(15 citation statements)

References 55 publications

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“…Because the proteolipid is an intrinsic membrane protein, it presumably participates in lipid-protein interactions important for the maintenance of bilayer integrity. However, a portion of the protein is at the surface of the membrane, where it can interact with the extracellular environment [2]. In particular, immunocompetent cells specifically sensitized to the proteolipid might interact with these exposed regions.…”

Section: Time Post Immunizationmentioning

confidence: 99%

Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: Immunological studies in rabbits

Cambi

Lees

Williams

et al. 1983

Annals of Neurology

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A chronic experimental allergic encephalomyelitis (EAE) has been produced in rabbits sensitized with bovine white matter proteolipid apoprotein. Eleven of 12 animals developed clinical disease one to six months after immunization with a single dose of the apoprotein. The clinical course was characterized by posterior ataxia, flaccid paralysis progressing to spastic paralysis, and incontinence. Spontaneous relapses and remissions were observed in 3 rabbits. Histologically, acute and chronic encephalomyelitis accompanied by primary demyelination were observed. Serum antibody production, assayed by both an enzyme-linked immunosorbent assay and an electroblot procedure, did not correlate with either the clinical course or the histopathological findings. Delayed hypersensitivity to proteolipid apoprotein was observed in all rabbits prior to the onset of clinical signs. The data suggest that lymphocytes specifically sensitized to the proteolipid may be involved in the pathogenesis of the demyelination in chronic EAE.

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Section: Time Post Immunizationmentioning

confidence: 99%

Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: Immunological studies in rabbits

Cambi

Lees

Williams

et al. 1983

Annals of Neurology

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“…When all these various experimental results are taken together, and further considered in the light of an observed ability of the basic protein to induce a cross-linking of lipid bilayers in vitra (Smith, 1977b), I believe they support my original hypothesis that the MBP plays an important role in the interfacing of the cytoplasmic bilayer surfaces in the CNS (Braun, 1977).…”

Section: Cns Myelin Proteinsmentioning

confidence: 57%

“…Cytochemical and biochemical methods have detected BP at either the cytoplasmic or extracellular interfaces (Golds and Braun, 1976;Mendell and Whitaker, 1978; for earlier studies, see the review by Braun, 1977). These methods either introduce substantial perturbation in the myelin structure or may be limited by incomplete penetration of labels.…”

Section: Basic Proteinmentioning

confidence: 99%

“…Basic proteins (BPs) have been proposed as "structural cement" in myelin formation and stabilization (Carnegie and Dunckley, 1975;Braun, 1977). The experimental basis of this proposal has been critically reviewed by , who concluded that BP does not contribute significantly to myelin stability.…”

Section: Ditance Between Membran •• (A)mentioning

confidence: 99%

“…That is, an elaborate model that defines detailed maeromoleeular conformations and speeifie protein-lipid interactions remains an unfulfilled objeetive. Nevertheless, suffieient information exists to provide at least a refinement of previously published models (Braun, 1977;Boggs et al, 1982). Figures 2 and 3, then, are an attempt to summarize in diagrammatic fashion our current understanding of the probable protein organization in myelin bilayers.…”

Section: A Myelin Modelmentioning

confidence: 99%

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Myelin

1984

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Insertion of proteolipid protein into oligodendrocyte mitochondria regulates extracellular pH and adenosine triphosphate

Appikatla

Bessert

Lee

et al. 2013

Glia

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Proteolipid protein (PLP) and DM20, the most abundant myelin proteins, are coded by the human PLP1 and non-human Plp1 proteolipid protein gene. Mutations in the PLP1 gene cause Pelizaeus-Merzbacher Disease (PMD) with duplications of the native PLP1 gene accounting for 70% of PLP1 mutations. Humans with PLP1 duplications and mice with extra Plp1 copies have extensive neuronal degeneration. The mechanism that causes neuronal degeneration is unknown. We show that native PLP traffics to mitochondria when the gene is duplicated in mice and in humans. This report is the first demonstration of a specific cellular defect in brains of PMD patients; it validates rodent models as ideal models to study PMD. Insertion of nuclear-encoded mitochondrial proteins requires specific import pathways; we show that specific cysteine motifs, part of the Mia40/Erv1 mitochondrial import pathway, are present in PLP and are required for its insertion into mitochondria. Insertion of native PLP into mitochondria of transfected cells acidifies media, partially due to increased lactate; it also increases ATP in the media. The same abnormalities are found in the extracellular space of mouse brains with extra copies of Plp1. These physiological abnormalities are preventable by mutations in PLP cysteine motifs, a hallmark of the Mia40/Erv1 pathway. Increased extracellular ATP and acidosis lead to neuronal degeneration. Our findings may be the mechanism by which microglia are activated and pro-inflammatory molecules are up-regulated in Plp1 transgenic mice (Tatar et al., 2010). Manipulation of this metabolic pathway may restore normal metabolism and provide therapy for PMD patients.

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Molecular Architecture of Myelin

Cited by 39 publications

References 55 publications

Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: Immunological studies in rabbits

Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: Immunological studies in rabbits

Myelin

Insertion of proteolipid protein into oligodendrocyte mitochondria regulates extracellular pH and adenosine triphosphate

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