A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions
| Autor: | Wolfgang Brueck, Jack Rosenbluth, Glaucia C. Furtado, Joseph D. Buxbaum, Moses V. Chao, Joseph Schlessinger, Juan J. Lafaille, Sheila Harroch |
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| Rok vydání: | 2002 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Phosphoric monoester hydrolases Genotype Encephalomyelitis Mice Transgenic Nerve Tissue Proteins Cell Separation Protein tyrosine phosphatase Biology Mice In Situ Nick-End Labeling Genetics medicine Animals Humans Receptor In Situ Hybridization Autoimmune disease chemistry.chemical_classification Receptor-Like Protein Tyrosine Phosphatases Class 5 Multiple sclerosis Flow Cytometry medicine.disease Molecular biology Enzyme Spinal Cord chemistry PTPRZ1 Mutation Immunology Lymph Nodes Protein Tyrosine Phosphatases Cell Division |
| Zdroj: | Nature Genetics. 32:411-414 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng1004 |
| Popis: | Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease. |
| Databáze: | OpenAIRE |
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