Proteolipid Protein Is Necessary in Peripheral as Well as Central Myelin

Garbern, James; Cambi, Franca; Tang, Xue; Sima, Anders A. F.; Vallat, Jean Michel; Bosch, E. Peter; Lewis, Richard A.; Shy, Michael E.; Sohi, Jasloveleen; Kraft, George H.; Chen, Ke Lian; Joshi, Indira; Leonard, Debra G.B.; Johnson, William G.; Raskind, Wendy H.; Dlouhy, Stephen R.; Pratt, Victoria M.; Hodes, M. E.; Bird, Thomas D.; Kamholz, John

doi:10.1016/s0896-6273(00)80360-8

Cited by 145 publications

(130 citation statements)

References 68 publications

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“…The relative importance of each of these molecules has been further proven by studies with mice deficient in each of these molecules. Thus, as expected, lack of Po in humans and mice causes demyelination in the PNS (Giese et al, 1992;Su et al, 1993), while mutations of the Plp gene have been shown to cause Pelizaeus-Merzbacher disease, spastic paraplegia type 2 and demyelinating disorders in a range of animal species (Garbern et al, 1997;Griffiths et al, 1995;Shy et al, 2003). Both of these proteins are responsible for the compaction of the intraperiod line of myelin which corresponds to two extracellular layers of plasma membranes adhering in a zipper manner (Shapiro et al, 1996).…”

Section: The Myelin Questionmentioning

confidence: 62%

Glial cells: Old cells with new twists

Ndubaku

Bellard

2008

Acta Histochemica

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SummaryBased on their characteristics and function -migration, neural protection, proliferation, axonal guidance and trophic effects -glial cells may be regarded as probably the most versatile cells in our body. For many years, these cells were considered as simply support cells for neurons. Recently, it has been shown that they are more versatile than previously believed -as true stem cells in the nervous system -and are important players in neural function and development. There are several glial cell types in the nervous system: the two most abundant are oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Although both of these cells are responsible for myelination, their developmental origins are quite different. Oligodendrocytes originate from small niche populations from different regions of the central nervous system, while Schwann cells develop from a stem cell population (the neural crest) that gives rise to many cell derivatives besides glia and which is a highly migratory group of cells.

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Section: The Myelin Questionmentioning

confidence: 62%

Glial cells: Old cells with new twists

Ndubaku

Bellard

2008

Acta Histochemica

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“…To explore the molecular components of the remyelination program, we applied AGCA to the peripheral nerve crush and transection injury expression profiles. Because MPZ, PMP22, MBP, MAG, periaxin, proteolipid protein (PLP), and the DM20 variant of PLP have all been shown to be critical for myelination, these genes, which we designate myelin gene anchors (MGAs), were chosen as anchors to identify other genes involved in the myelination process (1,22,23).…”

Section: Resultsmentioning

confidence: 99%

Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Nagarajan

Le²,

Mahoney³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

124

131

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Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs, MASR (myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.

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“…23 A mild PMD3 phenotype has been also reported for the other two nonsense mutations described in the first coding bases ATGG (delG3, delG4). 24,25 The mutation at the end of exon 3A (ACA-AAA) has been classified as a form of SPG. 26 This PLP mutation outside exon 3B may be responsible for a T115K amino acid substitution in PLP/DM20 but may also disturb the splicing of exon 3 resulting in the absence of DM20.…”

Section: Discussionmentioning

confidence: 99%

Genotype–phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations

et al. 2000

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Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2) are X-linked developmental defects of myelin formation affecting the central nervous system (CNS). They differ clinically in the onset and severity of the motor disability but both are allelic to the proteolipid protein gene (PLP), which encodes the principal protein components of CNS myelin, PLP and its spliced isoform, DM20. We investigated 52 PMD and 28 SPG families without large PLP duplications or deletions by genomic PCR amplification and sequencing of the PLP gene. We identified 29 and 4 abnormalities respectively. Patients with PLP mutations presented a large range of disease severity, with a continuum between severe forms of PMD, without motor development, to pure forms of SPG. Clinical severity was found to be correlated with the nature of the mutation, suggesting a distinct strategy for detection of PLP point mutations between severe PMD, mild PMD and SPG. Single amino-acid changes in highly conserved regions of the DM20 protein caused the most severe forms of PMD. Substitutions of less conserved amino acids, truncations, absence of the protein and PLP-specific mutations caused the milder forms of PMD and SPG. Therefore, the interactions and stability of the mutated proteins has a major effect on the severity of PLP-related diseases.

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Proteolipid Protein Is Necessary in Peripheral as Well as Central Myelin

Cited by 145 publications

References 68 publications

Glial cells: Old cells with new twists

Glial cells: Old cells with new twists

Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Genotype–phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations

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