Elucidation of the molecular mechanisms of anti-ganglioside antibody-induced neuronal dysfunction

以往的研究表明，抗神经节苷脂抗体，如抗GM1抗体已被假定为具有病理学意义的发展，临床GBS样表型。目前，这些抗神经节苷脂抗体的分子机制和意义尚不清楚。在该项目中，我们检测了这些抗体对高亲和力神经生长因子（NGF）受体Trk功能的分子效应，并公开如下：1）抗GM1抗体对Trk活性的影响不同，有的增强了NGF诱导的Trk自磷酸化，有的抑制了。2）在全细胞培养体系中，这些抗体阳性血清不同地刺激参与细胞内信号转导级联的细胞内信号分子。这些数据表明，来自不同患者的抗GM1抗体并不总是相同的，它影响Trk介导的细胞内信号传导机制的功能。

Previous studies have shown that anti-ganglioside antibody such as anti-GM1 antibody has been postulated to have the pathognomonic implication for the development of clinical GBS-like phenotype. At present, however, the detailed molecular mechanisms and significances of these anti-ganglioside antibodies. In this project, we examined the molecular effects of these antibodies on the function of high affinity nerve growth factor (NGF) receptor, Trk and disclosed as follows ; 1)anti-GM1 antibodies differently affected the function of Trk activity among these antibodies, some augmented NGF-induced Trk autophosphorylation, the other inhibited it. 2)In whole cell culture system, these antibody-positive sera differently stimulated the intracellular signaling molecules that are involved in the intracellular signal transduction cascade. These data suggested that anti-GM1 antibody from different patients is not always identical and it affected the function of Trk-mediated intracellular signaling machinery.