Hauser Stephen L, Oksenberg Jorge R
Department of Neurology, School of Medicine, University of California at San Francisco, San Francisco, California 94143, USA.
Neuron. 2006 Oct 5;52(1):61-76. doi: 10.1016/j.neuron.2006.09.011.
The autoimmune model of multiple sclerosis (MS) pathogenesis provided for many years a useful but incomplete conceptual framework for understanding the complex array of factors that lead to the loss of immune homeostasis, myelin and axonal injury, and progressive neurological symptoms. The availability of novel tools in molecular neurogenetics and increasingly sophisticated neuroimaging technologies, together with the revitalization of MS neuropathology, has created a new paradigm for the multidisciplinary study of this disease. This is reflected by the growing resolution of the MS genomic map, discovery of delicate inflammatory networks that are perturbed in MS, identification of mediators of demyelination, and recognition that cumulative axonal loss and neuronal injury are the histological correlates of neurological disability. Together, these advances have set the stage for the development of therapeutic approaches designed to target the demyelinating and neurodegenerative components of the disease and promote repair.
多年来，多发性硬化症（MS）发病机制的自身免疫模型为理解导致免疫稳态丧失、髓鞘和轴突损伤以及进行性神经症状的复杂因素提供了一个有用但不完整的概念框架。分子神经遗传学领域新工具的出现以及日益复杂的神经成像技术，再加上MS神经病理学的复兴，为该疾病的多学科研究创造了一个新的范式。这体现在MS基因组图谱分辨率的不断提高、对MS中受到干扰的精细炎症网络的发现、脱髓鞘介质的鉴定，以及认识到累积的轴突损失和神经元损伤是神经功能障碍的组织学相关因素。这些进展共同为开发旨在针对该疾病的脱髓鞘和神经退行性成分并促进修复的治疗方法奠定了基础。
