Imitola Jaime, Chitnis Tanuja, Khoury Samia J
Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Arch Neurol. 2006 Jan;63(1):25-33. doi: 10.1001/archneur.63.1.25.
Despite recent advances in the diagnosis and treatment of multiple sclerosis, we still lack a consensus regarding the causes, pathogenesis, and mechanisms of disease progression. Current evidence indicates that multiple sclerosis is an inflammatory neurodegenerative disorder in which both adaptive and innate immunity play important roles in initiation and maintenance of the disease. Recent evidence supports the notion of molecular pathologic abnormalities beyond the plaques and dysfunction of neurons in normal appearing areas, in addition to the multifocal demyelination and axonal loss, as important features that may underlie early reversible changes in the disease. Chronic failure of remyelination, axonal regeneration, and neuronal dysfunction may contribute to disease progression. This article discusses the emerging molecular evidence for the progression of multiple sclerosis with particular focus on alterations in the local central nervous system microenvironment of neural and glial cells. The molecular pathways leading to structural and functional neurodegeneration and those that prevent regeneration need to be identified in order to design new therapeutic strategies that can halt or even reverse disease progression.
尽管近年来在多发性硬化症的诊断和治疗方面取得了进展，但我们在该疾病的病因、发病机制和疾病进展机制方面仍未达成共识。目前的证据表明，多发性硬化症是一种炎症性神经退行性疾病，其中适应性免疫和先天性免疫在疾病的起始和维持中均起重要作用。最近的证据支持这样一种观点，即除了多灶性脱髓鞘和轴突丢失外，斑块以外的分子病理异常以及正常外观区域的神经元功能障碍，也是该疾病早期可逆性变化的重要潜在特征。髓鞘再生、轴突再生的长期失败以及神经元功能障碍可能导致疾病进展。本文讨论了多发性硬化症进展的新出现的分子证据，特别关注神经和胶质细胞局部中枢神经系统微环境的改变。为了设计能够阻止甚至逆转疾病进展的新治疗策略，需要确定导致结构和功能性神经退行性变的分子途径以及那些阻止再生的途径。
