The heat shock response modulates transthyretin deposition in the peripheral and autonomic nervous systems
The heat shock response modulates transthyretin deposition in the peripheral and autonomic nervous systems
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DOI：
10.1016/j.neurobiolaging.2008.04.001
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发表时间：
2010-02-01
影响因子：
4.2
通讯作者：
Saraiva, Maria Joao
中科院分区：
文献类型：
--
作者：
Santos, Sofia Duque;Fernandes, Rui;Saraiva, Maria Joao
家族性淀粉样变性多发性神经病（FAP）是一种选择性影响周围神经系统的神经退行性疾病。这种危及生命的病理的假定原因是突变甲状腺素（TTR）的组织沉积，最初为非纤维沉积，后来为纤维物质。目前可用的小鼠模型不能再现人类的全部特征，因为周围神经组织没有被保留。我们在热休克转录因子1 （Hsf1）为零的背景下建立了一种表达人甲状腺素V30M的小鼠模型。HSF1表达的缺乏导致广泛和早期的非纤维性TTR，在包括周围神经系统在内的不同器官中演变成纤维物质。此外，与人类患者一样，观察到炎症应激和无髓神经纤维的减少。这些结果表明HSF1调节基因参与FAP，调节FIR组织沉积。这种新的小鼠模型对于测试新的治疗策略和解决应激反应对错误折叠疾病的影响至关重要。(C) 2008爱思唯尔公司版权所有。
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease that selectively affects the peripheral nervous system. The putative cause of this life threatening pathology is tissue deposition of mutant transthyretin (TTR), initially as non-fibrillar deposits and later as fibrillar material. The mouse models currently available do not recapitulate the human whole features, since the peripheral nervous tissue is spared. We have characterized a new mouse model expressing the human transthyretin V30M in a heat shock transcription factor 1 (Hsf1) null background. The lack of HSF1 expression leads to an extensive and earlier non-fibrillar TTR, evolving into fibrillar material in distinct organs including the peripheral nervous system. Furthermore, inflammatory stress and a reduction in unmyelinated nerve fibers were observed, as in human patients. These results indicate that HSF1 regulated genes are involved in FAP, modulating FIR tissue deposition. The novel mouse model is of the utmost importance in testing new therapeutic strategies and in addressing the influence of the stress response in misfolding diseases. (C) 2008 Elsevier Inc. All rights reserved.