Molecular Biology of Motor Neuron Disease

虽然怀疑自身抗体的参与，但运动神经元疾病的病因尚未确定。在许多情况下，检测到高滴度的抗体，特别是针对鞘糖脂的抗体。鞘糖脂是神经系统的膜成分，其表达随细胞、分化和细胞生长的不同而不同。通常，抗糖脂的自身抗体与神经细胞发生反应，损害神经功能。在本研究项目中，我们展示了糖脂在神经系统中的特征性分布，并且这些糖脂的表达可以通过引入糖脂代谢相关酶的基因来调节。在神经系统疾病发病前经常观察到肠炎等感染，我们发现先前感染的微生物与神经系统的鞘糖脂表现出分子拟态。从免疫学和化学上证实了几种空肠梭菌脂多糖与各种神经节苷类之间的分子相似性。抗硫酸葡糖醛基糖脂的抗体伴或不伴m蛋白血症也与神经系统反应。这些对神经系统的反应在形态学、免疫学和电生理学上都得到了证实，并通过单克隆抗体和患者体内血清以及体外血神经屏障人工模型进行了证实。我们可以提出证据表明，抗糖脂抗体是在发病前由感染产生的，由于微生物和神经系统结构成分之间的分子相似性，这种抗体损害神经系统。

Although the participation of the autoantibody is suspected, the etiology of the motor neuron diseases is not yet established.In many cases high titer of antibodies, especially against to glycosphingolips, are detected. Glycosphingolipds are the membrane components of the nervous system, and their expression is different dependent on cells, differentiation, and cell growth. Frequently, autoantibodies against glycolipds reacted with the nervous cells and damaged the nervous functions.In this research project we show the characteristic distribution of the glycolipids in the nervous system, and the expression of these glycolipids can be modulated by the introduction of the genes of the enzymes related to the metabolism of glycolipids.Infections such as enteritis are frequently observed before the onset of the neural diseases, and we found that the microbes of the previous infection show the molecular mimicry with the sphingoglycolipids of the nervous system. These molecular mimicry between the lipopolysaccharides of several strains of C.jejuni and various kinds of gangliosides are proved immunologically and chemically.Antibodies against sulfated glucuronyl glycolipids with or without M-proteinemia also reacted with nervous system. These reactions to the nervous system is confirmed morphologically, immunologically and electrophysiologically with the monoclonal antibody and also sera from the patients in vivo and also in vitro using the artificial model of blood-nerve barrier.We can present the evidence that the anti-glycolipid antibody is produced by infection before the onset of disease, and this antibody damages the nerous system due to the molecular mimicry between the microbes and structural components of the nervou system.