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多发性硬化症非损伤性灰质中轴突运动蛋白表达降低。

Reduced axonal motor protein expression in non-lesional grey matter in multiple sclerosis.

作者信息

Hares K, Kemp K, Rice C, Gray E, Scolding N, Wilkins A

机构信息

Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, UK

Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, UK.

出版信息

Mult Scler. 2014 Jun;20(7):812-21. doi: 10.1177/1352458513508836. Epub 2013 Oct 21.

Abstract

BACKGROUND

Multiple sclerosis (MS) is a neurological disease characterised by central nervous system inflammation, demyelination, axonal degeneration and neuronal injury. Preventing neuronal and axon damage is of paramount importance in attempts to prevent disease progression. Intact axonal transport mechanisms are crucial to axonal integrity and evidence suggests these mechanisms are disrupted in MS. Anterograde axonal transport is mediated to a large extent through the kinesin superfamily proteins. Recently, certain kinesin superfamily proteins (KIF5A, KIF1B and KIF21B) were implicated in MS pathology.

OBJECTIVES

To investigate the expression of KIF5A, KIF21B and KIF1B in MS and control post-mortem grey matter.

METHODS

Using both quantitative real-time polymerase chain reaction (PCR) and Immunodot-blots assays, we analysed the expression of kinesin superfamily proteins in 27 MS cases and 13 control cases not linked to neurological disease.

RESULTS

We have shown significant reductions in KIF5A, KIF21B and KIF1B messenger ribonucleic acid (mRNA) expression and also KIF5A protein expression in MS grey matter, as compared to control grey matter.

CONCLUSION

We have shown significant reductions in mRNA and protein levels of axonal motor proteins in the grey matter of MS cases, which may have important implications for the pathogenesis of neuronal/axonal injury in the disease.

摘要

背景

多发性硬化症(MS)是一种神经系统疾病,其特征为中枢神经系统炎症、脱髓鞘、轴突变性和神经元损伤。在预防疾病进展的尝试中,防止神经元和轴突损伤至关重要。完整的轴突运输机制对轴突完整性至关重要,且有证据表明这些机制在MS中受到破坏。顺向轴突运输在很大程度上是通过驱动蛋白超家族蛋白介导的。最近,某些驱动蛋白超家族蛋白(KIF5A、KIF1B和KIF21B)与MS病理学有关。

目的

研究KIF5A、KIF21B和KIF1B在MS及对照尸检灰质中的表达。

方法

我们使用定量实时聚合酶链反应(PCR)和免疫斑点印迹分析,分析了27例MS病例和13例与神经系统疾病无关的对照病例中驱动蛋白超家族蛋白的表达。

结果

与对照灰质相比,我们发现MS灰质中KIF5A、KIF21B和KIF1B信使核糖核酸(mRNA)表达以及KIF5A蛋白表达均显著降低。

结论

我们发现MS病例灰质中轴突运动蛋白的mRNA和蛋白水平显著降低,这可能对该疾病中神经元/轴突损伤的发病机制具有重要意义。

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