Death receptor 6 negatively regulates oligodendrocyte survival, maturation and myelination
| Autor: | Lee Walus, Yinghui Hu, R. Blake Pepinsky, Guanrong Huang, Zhaohui Shao, Xinhua Lee, Bang Jian Gong, Robert H. Miller, Sha Mi, Benxiu Ji, Weixing Yang, Kenneth J. Rhodes |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Multiple Sclerosis Cell Survival Encephalomyelitis Central nervous system Blotting Western General Biochemistry Genetics and Molecular Biology Receptors Tumor Necrosis Factor Myelin Mice medicine Animals Remyelination Myelin Sheath biology Caspase 3 Reverse Transcriptase Polymerase Chain Reaction Multiple sclerosis Experimental autoimmune encephalomyelitis Cell Differentiation General Medicine medicine.disease Oligodendrocyte Myelin basic protein Cell biology Rats Enzyme Activation Oligodendroglia medicine.anatomical_structure Gene Expression Regulation Immunology biology.protein |
| Zdroj: | Nature medicine. 17(7) |
| ISSN: | 1546-170X |
| Popis: | Survival and differentiation of oligodendrocytes are important for the myelination of central nervous system (CNS) axons during development and crucial for myelin repair in CNS demyelinating diseases such as multiple sclerosis. Here we show that death receptor 6 (DR6) is a negative regulator of oligodendrocyte maturation. DR6 is expressed strongly in immature oligodendrocytes and weakly in mature myelin basic protein (MBP)-positive oligodendrocytes. Overexpression of DR6 in oligodendrocytes leads to caspase 3 (casp3) activation and cell death. Attenuation of DR6 function leads to enhanced oligodendrocyte maturation, myelination and downregulation of casp3. Treatment with a DR6 antagonist antibody promotes remyelination in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis (EAE) models. Consistent with the DR6 antagoinst antibody studies, DR6-null mice show enhanced remyelination in both demyelination models. These studies reveal a pivotal role for DR6 signaling in immature oligodendrocyte maturation and myelination that may provide new therapeutic avenues for the treatment of demyelination disorders such as multiple sclerosis. |
| Databáze: | OpenAIRE |
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