Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Biochem Biophys Res Commun. 2010 Feb 19;392(4):551-6. doi: 10.1016/j.bbrc.2010.01.062. Epub 2010 Jan 25.
Alpha-/beta-dystroglycans (DG) located at the outmost layer of myelin sheath play a critical role in its formation and stability in the peripheral nerve system. The demyelination of nerve fibers is present in autoimmune neuritis, however, it is not known about the molecular mechanisms underlying this pathological process. In an animal model of experimental autoimmune neuritis, we observed that beta-DG cleavage was associated with the demyelination of peripheral nerves. The neuritis and beta-DG cleavage were accompanied by matrix metalloproteinase (MMP)-2/-9 over-expressions and attenuated by captopril, a MMP inhibitor. The blockade of MMPs also improves clinical signs. Our results reveal a crucial role of MMP-mediated beta-DG cleavage in autoimmune neuritis, such as Guillain-Barre' syndrome, and bring insights into therapeutic strategies for autoimmune diseases.
位于髓鞘最外层的α/β- 连接素（DG）在周围神经系统的形成和稳定中起着关键作用。在自身免疫性神经炎中存在神经纤维脱髓鞘，但尚不清楚该病理过程的分子机制。在实验性自身免疫性神经炎的动物模型中，我们观察到β-DG 裂解与周围神经脱髓鞘有关。神经炎和β-DG 裂解伴随着基质金属蛋白酶（MMP）-2/-9 的过度表达，并被 MMP 抑制剂卡托普利减弱。MMP 的阻断也改善了临床症状。我们的研究结果揭示了 MMP 介导的β-DG 裂解在自身免疫性神经炎中的关键作用，如格林-巴利综合征，并为自身免疫性疾病的治疗策略提供了新的见解。
