THY-1 RECEPTOR AND CNS NEURITE REGENERATION

THY-1 受体和 CNS 神经突再生

• 批准号: 3084406
• 负责人: EVAN B. DREYER
• 金额: $ 8.57万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084406
• 关键词: antibody; antiidiotype antibody; antireceptor antibody; brain cell; central nervous system; chemical synthesis; enzyme linked immunosorbent assay; growth cones; immunofluorescence technique; laboratory mouse; laboratory rat; monoclonal antibody; myelin glycoprotein; nervous system regeneration; neurogenesis; neurons; neuropeptide receptor; protein structure function; radiopharmacology; radiotracer; receptor binding; tissue /cell culture; western blottings

If nerve cells in the central nervous system could regenerate their processes (axons and dendrites), it would become possible to treat injuries to these processes due, for example, to stroke. This proposal describes one class of substances that has recently been recognized to be important in regeneration in the mammalian central nervous system because of work in tissue culture and in vivo. Thy-1 is the most abundant glycoprotein in rat neurons; homologues have been identified in species from invertebrates to man. Specific Thy-1 antibodies have been shown to promote regeneration of processes (also termed neurites) by mammalian retinal ganglion cells. Thy-1 antibodies have, as well, promoted optic nerve growth after transection. The growth of other types of central neurons also appears to be influenced by these antibodies (nearly all neurons have Thy-1 glycoprotein on their surface membrane). It is therefore proposed that there exists a naturally occurring Thy-l-receptor that is analogous to the Thy-1 antibodies. This Thy-1-receptor may influence the outgrowth and regeneration of neuronal processes by central mammalian neurons, such as retinal ganglion cells, by binding to the Thy-1 molecule on the surface of neurons in the same way that the Thy-1 antibody does. The current grant proposes to purify an endogenous Thy-l-receptor by using as probes two monoclonal anti-idiotype antibodies against Thy-1 antibodies and a recently purified form of the Thy-1 molecule. The Thy-l-receptor has already been tentatively identified in preliminary experiments using immunofluorescence techniques, isoelectric focusing, and molecular biological approaches. The presence of a homologue of Thy-1 on human CNS neurons indicates that these studies may have relevance to the problem of CNS regeneration after stroke in man.

如果中枢神经系统中的神经细胞能够再生， 过程（轴突和树突），它将成为可能治疗损伤 例如中风引起的这些过程。该提案描述了一个 一类物质，最近被认为是重要的， 哺乳动物中枢神经系统的再生， 组织培养和体内。 Thy-1是大鼠体内最丰富的糖蛋白 神经元;同系物已被确定在物种从无脊椎动物， 伙计特异性Thy-1抗体已经显示出促进细胞再生。 突起（也称为神经突）的哺乳动物视网膜神经节细胞。 Thy-1抗体也促进了视神经的生长， 横切其他类型的中枢神经元的生长似乎也 受这些抗体的影响（几乎所有的神经元都有Thy-1 在其表面膜上的糖蛋白）。因此提议 存在天然存在的Thy-1受体，其类似于 Thy-1抗体。这种Thy-1受体可能会影响生长， 中枢哺乳动物神经元的神经元过程的再生，例如 视网膜神经节细胞，通过结合到Thy-1分子的表面上， Thy-1抗体对神经元的作用。当前许可 提出了通过使用两个探针纯化内源性Thy-1受体， 抗Thy-1抗体的单克隆抗独特型抗体， Thy-1分子的纯化形式。Thy-1受体已经被 在初步实验中使用免疫荧光初步鉴定 技术、等电聚焦和分子生物学方法。的 Thy-1同源物在人CNS神经元上的存在表明， 研究可能与中风后中枢神经系统再生的问题有关 在人身上。