Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability
Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability
复制标题
DOI：
10.1016/s0165-5728(01)00455-6
复制
发表时间：
2002-01-01
影响因子：
3.3
通讯作者：
Sharief, MK
中科院分区：
文献类型：
--
作者：
Semra, YK;Seidi, OA;Sharief, MK
多发性硬化症(MS)疾病进展的病理基础被认为涉及轴突变性，轴突变性有助于神经功能障碍的积累。最近的报道表明，复发缓解期多发性硬化症患者鞘内神经丝蛋白的浓度与疾病活动性和残疾程度有关。我们试图调查进展性多发性硬化患者和相关对照组中其他轴突细胞骨架成分的鞘内水平，主要是肌动蛋白、微管蛋白和神经细丝轻亚单位(NFL)，并将结果与疾病严重程度的临床参数相关联。与其他炎症性或非炎症性神经系统疾病患者相比，MS患者脑脊液中肌动蛋白、微管蛋白和神经营养因子的浓度显著升高。此外，与复发缓解性疾病患者相比，原发性和继发性进展性MS患者鞘内肌动蛋白和微管蛋白的释放以及较小程度的NFL的释放明显更明显，并与临床残疾相关。我们的发现提示进行性MS与鞘内轴突细胞骨架蛋白释放增加有关，而脑脊液肌动蛋白、微管蛋白和NFL是轴突损伤的可靠标记物。(C)2002 Elsevier Science B.V.保留所有权利。
The pathologic basis of disease progression in multiple sclerosis (MS) is thought to involve axonal degeneration, which contributes to the accumulation of neurological disability. Recent reports suggest that intrathecal concentrations of the neurofilament protein in relapsing remitting MS correlate with disease activity and the degree of disability. We sought to investigate the intrathecal levels of other cytoskeletal components of axons, primarily actin, tubulin and the light subunit of neurofilament (NFL) in patients with progressive MS and relevant controls and correlate results with clinical parameters of disease severity. Cerebrospinal fluid (CSF) concentrations of actin, tubulin and NFL were significantly increased in MS patients when compared to corresponding levels in patients with other inflammatory or non-inflammatory neurological diseases. Moreover, the intrathecal release of actin and tubulin, and to a lesser extent NFL, was significantly more marked in patients with primary and secondary progressive MS when compared to patients with relapsing remitting disease and was correlated with clinical disability. Our findings suggest that progressive MS is associated with the heightened intrathecal release of axonal cytoskeletal proteins, and that CSF actin, tubulin and NFL are reliable markers of axonal damage. (C) 2002 Elsevier Science B.V. All rights reserved.