HSPB3 protein is expressed in motoneurons and induces their survival after lesion-induced degeneration
HSPB3 protein is expressed in motoneurons and induces their survival after lesion-induced degeneration
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DOI：
10.1016/j.expneurol.2016.08.014
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发表时间：
2016-12-01
影响因子：
5.3
通讯作者：
Krieglstein, Kerstin
中科院分区：
文献类型：
--
作者：
La Padula, Veronica;Staszewski, Ori;Krieglstein, Kerstin
人类小分子热休克蛋白(HSPB)是一个由10个成员(HSPB1-HSPB10)组成的分子伴侣家族，其功能从蛋白质质量控制到细胞骨架动力学和细胞死亡控制。HSPB的突变可导致人类疾病，尤其是HSPB1和HSPB8的点突变已知会导致周围神经疾病。最近，该家族的另一成员HSPB3的一个错义突变(R7S)被发现引起轴索性运动神经病(远端遗传性运动神经病2C型，dHMN2C)。因此，我们研究了内源性HSPB3蛋白在鸡和小鼠胚胎脊髓以及鸡、小鼠和人的出生后神经系统(中枢和外周)中的分布。我们进一步研究了野生型和突变型HSPB3通过在禽类MN变性的肢芽摘除动物模型中过表达对MN细胞死亡的影响。总之，我们的发现是更好地理解导致dHMN2C的细胞和分子机制的第一步。(C)2016年提交人。由爱思唯尔公司出版。
The human small heat shock proteins (HSPBs) form a family of molecular chaperones comprising ten members (HSPB1-HSPB10), whose functions span from protein quality control to cytoskeletal dynamics and cell death control. Mutations in HSPBs can lead to human disease and particularly point mutations in HSPB1 and HSPB8 are known to lead to peripheral neuropathies. Recently, a missense mutation (R7S) in yet another member of this family, HSPB3, was found to cause an axonal motor neuropathy (distal hereditary motor neuropathy type 2C, dHMN2C).Until now, HSPB3 protein localization and function in motoneurons (MNs) have not yet been characterized. Therefore, we studied the endogenous HSPB3 protein distribution in the spinal cords of chicken and mouse embryos and in the postnatal nervous system (central and peripheral) of chicken, mouse and human. We further investigated the impact of wild-type and mutated HSPB3 on MN cell death via overexpressing these genes in ovo in an avian model of MN degeneration, the limb-bud removal. Altogether, our findings represent a first step for a better understanding of the cellular and molecular mechanisms leading to dHMN2C. (C) 2016 The Authors. Published by Elsevier Inc.