The role of galanin in demyelinating disease

脑保护：多发性硬化症的一种新的治疗方法在多发性硬化症（MS）中，免疫系统错误地攻击大脑。免疫攻击破坏了髓鞘，这是大脑中电缆周围的保护层（脱髓鞘）。目前对MS的治疗仅部分有效，并通过减少这些攻击的数量和严重程度来发挥作用。然而，大多数患者的MS相关永久性残疾是由于进展性MS的发展，目前的治疗不能减少这种进展。据信，这种永久性残疾的一个主要原因是永久性髓鞘丢失。有趣的是，我们已经证明生长因子LIF是在MS样炎症期间由身体产生的，并且它通过直接保护髓鞘生成细胞来限制损伤。然而，在炎症期间，身体自身的LIF产生是次最大的，因为髓鞘保护可以通过给予额外的治疗性LIF来增强。这表明（1）大脑对有害炎症产生防御反应，（2）这种防御反应可以通过治疗来增强。因此，我们想确切地定义LIF如何增强髓鞘存活。我们已经测量了髓鞘产生细胞对LIF的反应，并发现它强烈刺激小蛋白甘丙肽的产生。我们现在将评估甘丙肽本身是否保护髓鞘和髓鞘生成细胞，我们将在分离的细胞和整个动物模型中测试这一点。如果甘丙肽的产生是身体试图限制MS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）可能成为多发性硬化症的主要新疗法。

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.