Mallucci Giulia, Peruzzotti-Jametti Luca, Bernstock Joshua D, Pluchino Stefano
Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, Wellcome Trust-MRC Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY, UK.
Department of Brain and Behavioural Sciences, National Neurological Institute C. Mondino, University of Pavia, 27100 Pavia, Italy.
Prog Neurobiol. 2015 Apr;127-128:1-22. doi: 10.1016/j.pneurobio.2015.02.003. Epub 2015 Mar 21.
Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one's genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis.
多发性硬化症是成年早期至中年期开始的慢性神经功能障碍的最常见病因之一。多发性硬化症本质上是特发性的，但越来越多的相关证据支持个体的遗传易感性、环境和免疫系统之间存在密切关联。多发性硬化症的症状主要表现为中枢神经系统白质内有髓神经纤维束完整性的破坏。然而，最近的研究也强调了灰质在多发性硬化症疾病病理生理学中迄今未得到充分重视的作用，在考虑不可逆损伤的积累和进行性残疾时，这可能尤为重要。本综述旨在通过分析白质和灰质病变病理学，全面概述多发性硬化症病程中炎症、胶质/神经元损伤和再生之间的相互作用。此外，我们描述了复发型和进展型多发性硬化症共同的病理机制，并分析了当前（以及未来）的治疗方法可能如何与其病理相互作用和/或干扰其病理过程。了解驱动疾病发病机制的假定机制对于制定有效的治疗策略以预防、减轻和治疗与多发性硬化症相关的各种疾病至关重要。
