Institute of Virology, Centre for Hygiene and Human Genetics, University of Göttingen, Kreuzbergring 57, 37075 Göttingen, Germany.
Inflammopharmacology. 2011 Aug;19(4):187-95. doi: 10.1007/s10787-011-0084-6. Epub 2011 May 6.
It has recently been suggested that, rather than being an autoimmune disease, multiple sclerosis (MS) is an example of a neurocristopathy, a pathological process resulting from a faulty development of the neural crest. Whilst several characteristics of the disease suggest a neurocristopathy, other aetiological factors require consideration, including hygiene-related factors that alter the immune responses to common pathogens resulting in an eclipse of immune reactivity that could protect against MS, the possible role of human endogenous retroviruses (HERVs) in pathogenesis and autoimmune phenomena, HLA polymorphism, vitamin D levels before and after birth and immune repair mechanisms. A postulated aetiological factor in MS, associated with altered vitamin D metabolism and abnormal HERV expression, is a long-lasting disturbed redox regulation in the biosynthesis of a melanoma-like melanin pigment. Although intensive further studies on melanin pigments in nerve tissue in MS are required, the known properties of a pathological form of such pigments in melanoma could explain a number of observations in MS, including the impact of light, UV-light, and vitamin D, and could explain the clinical manifestations of MS on the basis of an oscillating process of oxidative charge and discharge of the pigments and a threshold phenomenon with a change of the quasi-catalytic function of the pigment from destroying reactive oxygen radicals or species to transforming them to more harmful long-persisting highly reactive species. Taken together with the consequences of an adaptive process in partly demyelinated neurons, resulting in an increase in number of mitochondria, and the impact of stressful life events, these conditions are necessary and sufficient to explain the disease process of MS with its spatial (plaques) and temporal (attacks and remissions) characteristics. This suggested unifying concept of the pathogenesis of MS may open perspectives for prevention, diagnosis and therapy. In particular, prevention may be achieved by vaccinating against Epstein-Barr virus in early childhood.
最近有人提出，多发性硬化症（MS）不是自身免疫性疾病，而是神经嵴病的一个例子，是一种源自神经嵴发育异常的病理过程。虽然该疾病的几个特征表明其是神经嵴病，但还需要考虑其他病因因素，包括改变常见病原体免疫反应的卫生相关因素，从而导致免疫反应受到抑制，可能对 MS 起到保护作用、人内源性逆转录病毒（HERV）在发病机制和自身免疫现象中的可能作用、HLA 多态性、出生前后维生素 D 水平以及免疫修复机制。MS 中的一个假定病因因素与改变的维生素 D 代谢和异常 HERV 表达有关，是黑色素样黑色素生物合成中持久存在的氧化还原调节紊乱。尽管需要对 MS 神经组织中的黑色素颜料进行更深入的研究，但已知黑色素这种病理性形式的特性可以解释 MS 中的许多观察结果，包括光、UV 光和维生素 D 的影响，并可以根据颜料的氧化电荷和放电的振荡过程以及颜料准催化功能从破坏活性氧自由基或物质到转化为更有害的持久高反应性物质的转变来解释 MS 的临床表现。再加上部分脱髓鞘神经元中的适应性过程的后果，导致线粒体数量增加，以及生活应激事件的影响，这些条件对于解释 MS 的疾病过程（斑块的空间特征和发作和缓解的时间特征）是必要和充分的。这种 MS 发病机制的统一概念可能为预防、诊断和治疗开辟新的视角。特别是可以通过在儿童早期接种针对 Epstein-Barr 病毒的疫苗来进行预防。
