Crystallins and neuroinflammation: The glial side of the story.
Crystallins and neuroinflammation: The glial side of the story.
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DOI：
10.1016/j.bbagen.2015.05.023
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Fort PE
中科院分区：
文献类型：
--
作者：
Dulle JE;Fort PE
有大量证据支持多种疾病中破坏性神经炎症和神经退行性变的关联。这些病理现象之间的联系之一是伴侣蛋白作为神经保护和免疫调节剂的作用。伴侣蛋白在神经炎症部位高度表达，无论是在神经胶质细胞还是在启动免疫反应的受损神经元中。由于这个原因，使用伴侣作为治疗与神经炎症相关的各种疾病是一个高度活跃的研究领域。这篇综述探讨了小热休克蛋白伴侣α-晶体蛋白影响神经胶质细胞功能的各种方式，特别关注它们在神经退行性疾病相关的炎症反应中的作用，以及它们作为治疗方法的潜力。尽管其机制仍在研究中，但α -晶体蛋白与神经炎症之间的明确联系已经建立，特别是通过它们在小胶质细胞和大胶质细胞中的作用。有趣的是，与炎症本身类似，晶体蛋白可以根据疾病的背景和持续时间对中枢神经系统产生有益或有害的影响。综上所述，本文指出了α -晶体蛋白等伴侣蛋白在经典蛋白折叠途径之外的新作用，以及它们在神经炎症/神经退行性疾病治疗新疗法开发中的潜力。
There is an abundance of evidence to support the association of damaging neuroinflammation and neurodegeneration across a multitude of diseases. One of the links between these pathological phenomena is the role of chaperone proteins as both neuroprotective and immune-regulatory agents. Chaperone proteins are highly expressed at sites of neuroinflammation both in glial cells and in the injured neurons that initiate the immune response. For this reason, the use of chaperones as treatment for various diseases associated with neuroinflammation is a highly active area of investigation. This review explores the various ways that the small heat shock protein chaperones, α-crystallins, can affect glial cell function with a specific focus on their implication in the inflammatory response associated with neurodegenerative disorders, and their potential as therapeutic treatment. Although the mechanisms are still under investigation, a clear link has now been established between alpha-crystallins and neuroinflammation, especially through their roles in microglial and macroglial cells. Interestingly, similar to inflammation in itself, crystallins can have a beneficial or detrimental impact on the CNS based on the context and duration of the condition. Overall this review points out the novel roles that chaperones such as alpha-crystallins can play outside of the classical protein folding pathways, and their potential in the development of new therapies for the treatment of neuroinflammatory/neurodegenerative diseases.