SNRP at Hunter College

亨特学院 SNRP

• 批准号: 7349989
• 负责人: Marie T. Filbin
• 金额: $ 26.6万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349989
• 关键词: culture; myelin; neurons; regeneration; university

The lack of regeneration in the adult mammalian central nervous system can be attributed, at least in part, to inhibitors of regeneration in myelin. To date 3 inhibitors have been identified and all 3 interact with the same receptor complex to effect inhibition. However, if neuronal cAMP is elevated, inhibition by myelin is blocked and regeneration is promoted in vivo. This cAMP effect is transcription-dependent and two genes that are up regulated are metallothionein-l/ll (MT-I/II) and secretory leukocyte protease inhibitor (SLPI). If added to neurons in culture, either of these two proteins allows neurons to grow on myelin. The immediate goals of the studies in this proposal are to a) Characterize and optimize the ability of MT-1/2 and SLPI to overcome myelin inhibitors in culture, b) Begin to address their mechanism of action by asking if they block the signal transduction pathway initiated by myelin inhibitors, c) Optimize conditions for in vivo delivery by assessing if neurons from animals treated with MT-1/2 or SLPI can grow in an inhibitory environment when cultured, and d) Determine if either MT-1/2 or SLPI can encourage dorsal column regeneration in vivo. The long-term objective is to determine if either MT-1/2 or SLPI can be developed as a therapy for patients with spinal cord injury.

成年哺乳动物中枢神经系统缺乏再生至少可以归因于 部分涉及髓鞘再生的抑制剂。到目前为止，已经确定了3种抑制剂， 与相同的受体复合物相互作用以实现抑制。然而，如果神经元cAMP升高， 髓磷脂的抑制作用被阻断，并在体内促进再生。这种cAMP效应是 转录依赖性和两个上调的基因是金属硫蛋白-I/II（MT-I/II）和 分泌性白细胞蛋白酶抑制剂（SLPI）。如果加入到培养的神经元中， 蛋白质让神经元在髓磷脂上生长。本建议中各项研究的近期目标是 a）表征和优化MT-1/2和SLPI克服髓磷脂抑制剂的能力， 文化，B）开始通过询问他们是否阻断信号来解决他们的作用机制 c）优化用于体内递送的条件， 评估来自用MT-1/2或SLPI处理的动物的神经元是否可以在抑制性生长中生长。 d）确定MT-1/2或SLPI是否可以促进背角化。 体内柱再生。长期目标是确定MT-1/2或SLPI是否可以 是为脊髓损伤患者开发的一种疗法。