研究人員發(fā)現(xiàn),，大腦中死亡受體DR6水平的上調(diào)將抑止多發(fā)性硬化癥患者大腦的修復(fù)。新成果發(fā)表在7月在線出版的《自然—醫(yī)學(xué)》（Nature Medicine）期刊上,，為多發(fā)性硬化癥的治療提供了一種潛在的新方法,。
多發(fā)性硬化癥患者會出現(xiàn)大規(guī)模的脫髓鞘反應(yīng)，神經(jīng)細(xì)胞軸突的保護層被損壞,，這也是患者出現(xiàn)神經(jīng)機構(gòu)衰退的原因之一,。Sha Mi和同事發(fā)現(xiàn)，多發(fā)性硬化癥患者大腦組織中死亡受體DR6水平被上調(diào)了,，他們在這種疾病的模擬小鼠中也發(fā)現(xiàn)了類似現(xiàn)象,。他們相信，DR6應(yīng)該是殺死不成熟突膠質(zhì)細(xì)胞的禍?zhǔn)郑荒z質(zhì)細(xì)胞是大腦中幫助修復(fù)受損髓磷脂的支持細(xì)胞,。
通過用抗體阻止多發(fā)性硬化癥模擬小鼠大腦中的死亡受體,，他們發(fā)現(xiàn)突膠質(zhì)細(xì)胞能夠修復(fù)受損的髓磷脂，并改善神經(jīng)機能障礙,。(生物谷 Bioon.com)
生物谷推薦原文出處：
Nature Medicine doi:10.1038/nm.2373
Death receptor 6 negatively regulates oligodendrocyte survival, maturation and myelination
Sha Mi; Xinhua Lee; Yinghui Hu; Benxiu Ji; Zhaohui Shao; Weixing Yang; Guanrong Huang; Lee Walus; Kenneth Rhodes; Bang Jian Gong; Robert H Miller; R Blake Pepinsky
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.
