14-3-3 proteins in Lewy body-like hyaline inclusions in patients with sporadic amyotrophic lateral sclerosis
14-3-3 proteins in Lewy body-like hyaline inclusions in patients with sporadic amyotrophic lateral sclerosis
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DOI：
10.1007/s00401-004-0923-2
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发表时间：
2004-12-01
影响因子：
12.7
通讯作者：
Budka, H
中科院分区：
文献类型：
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作者：
Kawamoto, Y;Akiguchi, I;Budka, H
14-3-3蛋白是高度保守的真核生物蛋白，通过磷酸化依赖的蛋白质-蛋白质相互作用调节各种类型的信号转导途径。14-3-3 mRNA在受损的大鼠运动神经元和肌萎缩性侧索硬化症（ALS）患者的脊髓中显示出上调。为了研究14-3-3蛋白在ALS中的作用，我们使用来自散发性ALS（sALS）患者和无脊髓受累的非ALS受试者的尸检脊髓对14-3-3进行了免疫组织化学研究。在两组的前角中，在运动神经元的胞体和近端突起中观察到强烈的14-3-3免疫反应性。来自所有sALS病例的许多球状体也是14-3-3免疫阳性。此外，路易小体样透明包涵体（LBHI），这是目前在一些sALS的情况下，强烈的免疫染色。我们的研究结果表明，即使在sALS患者严重受累的前角，剩余的运动神经元可能含有丰富的14-3-3蛋白，14-3-3蛋白可能与sALS的发病机制，特别是与LBHI的形成部分相关。
14-3-3 proteins are highly conserved eukaryotic proteins that regulate various types of signal transduction pathways through phosphorylation-dependent protein-protein interactions. 14-3-3 mRNAs have been shown to be up-regulated in the injured rat motor neurons and in the spinal cords of patients with amyotrophic lateral sclerosis (ALS). To investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical studies on 14-3-3 using autopsied spinal cords from patients with sporadic ALS (sALS) and non-ALS subjects without spinal cord involvement. In the anterior horn of both groups, strong 14-3-3 immunoreactivity was observed in the somata and proximal processes of motor neurons. Many spheroids from all of the sALS cases were also immunopositive for 14-3-3. In addition, Lewy body-like hyaline inclusions (LBHIs), which were present in some sALS cases, were intensely immunostained. Our findings suggest that even in the severely affected anterior horn of patients with sALS, remaining motor neurons may contain abundant 14-3-3 proteins, and that 14-3-3 proteins may be partly associated with the pathogenesis of sALS, in particular with the formation of LBHIs.