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

阐明抗神经节苷脂抗体诱导神经元功能障碍的分子机制

• 批准号: 17590902
• 负责人: MUTOH Tatsuro
• 金额: $ 2.24万
• 依托单位: FUJITA HEALTH UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590902/
• 关键词: signal transduction; GBS; nerve growth factor; Trk; tyrosine kinase; tyrosine phosphorylation; glucosylceramide; PC12 cells; GM1; チロシン自己燐酸化; 中性糖脂質; MAPK

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.

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GM 1抗体对Trk活性功能的影响不同，一些抗体增强了NGF诱导的Trk自磷酸化，另一些则抑制了它。2）在全细胞培养系统中，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。

项目成果

Acquired stuttering secondary to callosal infarction

继发于胼胝体梗死的获得性口吃

• 发表时间: 2005
• 期刊: Neurology 64
• 作者: Hamano T;Hiraki S;Kawamura Y;Mutoh T;kuriyama M
• 通讯作者: kuriyama M

Detection of new anti-neutral glycosphingolipids antibodies and their effects on Trk neurotrophin receptors

• DOI: 10.1016/j.febslet.2006.08.013
• 发表时间: 2006-09-18
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Mihara, T.;Ueda, A.;Mutoh, T.
• 通讯作者: Mutoh, T.

An post-infectious myeloradiculoneuropathy with cranial nerve Involvements associated Human Herpes virus type 7 infection

与人类疱疹病毒 7 型感染相关的感染后脊髓神经根神经病伴脑神经受累

• 发表时间: 2005
• 期刊: Arch Neurol 62
• 作者: Mihara T;Mutoh T^*;Yano S;Yoshikawa T;Asano Y;Yamamoto H
• 通讯作者: Yamamoto H

SIADH

抗利尿激素分泌异常综合征

• 发表时间: 2006
• 期刊: Clin Neurosci 24
• 作者: 三原貴照;武藤多津郎
• 通讯作者: 武藤多津郎

Role of glycosphingolipids and therapeutic perspectives on Alzheimer's disease

• DOI: 10.2174/187152706777950710
• 发表时间: 2006-08-01
• 期刊: CNS & Neurological Disorders-Drug Targets
• 影响因子: 3
• 作者: Mutoh, Tatsuro;Hirabayashi, Yoshio;Yamamoto, Hiroko
• 通讯作者: Yamamoto, Hiroko