The role of galanin in demyelinating disease

甘丙肽在脱髓鞘疾病中的作用

• 批准号: nhmrc : 454581
• 负责人: Prof Andrew Gundlach
• 金额: $ 22.34万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-galanin-demyelinating-disease/99209
• 关键词: role; galanin; demyelinating; disease

Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current therapies do not reduce this progression. It is believed that one major cause of this permanent disability is permanent myelin loss. Interestingly, we have already shown that the growth factor LIF is made by the body during MS-like inflammation, and that it limits damage by directly protecting myelin-producing cells. However, the bodies own LIF production during inflammation is sub-maximal, because myelin protection can be enhanced by giving additional therapeutic LIF. This suggests that (1) The brain produces a defence response to harmful inflammation and that (2) This defence response can be enhanced therapeutically. We therefore want to define exactly how LIF enhances myelin survival. We have measured the response to LIF in myelin-producing cells, and have discovered that it strongly stimulates the production of the small protein galanin. We will now assess if galanin itself protects myelin and myelin-producing cells, and we will test this both in isolated cells and whole animal models. If galanin production is a major mechanism by which the body tries to limit the damage from abnormal inflammation during MS, then medications that mimic the action of galanin (which are already under development for different reasons) could become a major new therapy for Multiple Sclerosis.

大脑保护：多发性硬化症的新治疗方法 在多发性硬化症 (MS) 中，免疫系统会错误地攻击大脑。免疫攻击会破坏髓磷脂，即大脑电缆周围的保护层（脱髓鞘）。目前对多发性硬化症的治疗仅部分有效，并且通过减少这些发作的次数和严重程度来发挥作用。然而，大多数患者与多发性硬化症相关的永久性残疾是由于进展性多发性硬化症的发展造成的，而目前的治疗方法并不能减少这种进展。据信，这种永久性残疾的主要原因之一是永久性髓鞘质丧失。有趣的是，我们已经证明生长因子 LIF 是由身体在 MS 样炎症期间产生的，并且它通过直接保护髓磷脂生成细胞来限制损伤。然而，炎症期间机体自身 LIF 的产生量低于最大水平，因为通过给予额外的治疗性 LIF 可以增强髓磷脂保护。这表明（1）大脑对有害炎症产生防御反应，并且（2）这种防御反应可以通过治疗得到增强。因此，我们想要准确定义 LIF 如何提高髓磷脂的存活率。我们测量了髓鞘生成细胞对 LIF 的反应，发现它强烈刺激小蛋白甘丙肽的生成。我们现在将评估甘丙肽本身是否可以保护髓磷脂和髓磷脂生成细胞，并且我们将在分离的细胞和整个动物模型中对此进行测试。如果甘丙肽的产生是身体试图限制多发性硬化症期间异常炎症造成的损害的主要机制，那么模仿甘丙肽作用的药物（由于不同的原因已经在开发中）可能会成为多发性硬化症的主要新疗法。