Toll-like receptors in neurodegeneration.
Toll-like receptors in neurodegeneration.
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DOI：
10.1016/j.brainresrev.2008.09.001
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发表时间：
2009-03
影响因子：
--
通讯作者：
Arumugam TV
中科院分区：
文献类型：
--
作者：
Okun E;Griffioen KJ;Lathia JD;Tang SC;Mattson MP;Arumugam TV
Toll样受体(Toll-like Receptor，TLRs)作为免疫细胞对入侵病原体的检测和应答的媒介，其关键作用是众所周知的。在哺乳动物中，至少有13种TLR是完整的膜蛋白，具有丰富的亮氨酸胞外区和类似于白细胞介素1受体的胞内区，后者通过激活酶启动下游信号，激活转录因子如AP-1和NFκB。TLR在神经胶质细胞(小胶质细胞、星形胶质细胞和少突胶质细胞)和淋巴细胞中被激活，这些细胞对感染性因素、组织损伤或自身免疫条件引起的炎症反应而渗透到神经系统。通过诱导免疫细胞产生促炎细胞因子和细胞黏附分子，TLRs可能会在缺血性中风和多发性硬化症等情况下间接损害神经元。最近的发现表明，神经元也表达TLRs的一个子集，在中风和阿尔茨海默病的实验模型中，它们的激活促进了神经元的退化。TLRs也可能在调节神经发生和轴突生长的过程中发挥作用，提示在神经元可塑性中发挥作用。更好地了解TLRs在正常和疾病神经系统中的分子和细胞生物学，可能会导致在一系列神经退行性疾病中预防神经元退变和促进功能恢复的新方法。
The key roles of toll-like receptors (TLRs) as mediators of the detection and responses of immune cells to invading pathogens are well known. There are at least 13 mammalian TLRs which are integral membrane proteins with a leucine-rich extracellular domain and a cytoplasmic domain similar to that of the interleukin-1 receptor which initiates downstream signaling through kinases to activate transcription factors such as AP-1 and NFκB. TLRs are activated in glial cells (microglia, astrocytes and oligodendrocytes) and lymphocytes that infiltrate the nervous system in response to inflammation caused by infectious agents, tissue injury or autoimmune conditions. By inducing the production of pro-inflammatory cytokines and cell adhesion molecules in immune cells, TLRs may indirectly damage neurons in conditions such as ischemic stroke and multiple sclerosis. Recent findings suggest that neurons also express a subset of TLRs and that their activation promotes neuronal degeneration in experimental models of stroke and Alzheimer’s disease. TLRs may also play roles in regulating the processes of neurogenesis and neurite outgrowth, suggesting roles in neuronal plasticity. A better understanding of the molecular and cellular biology of TLRs in the normal and diseases nervous system, may lead to novel approaches for preventing neuronal degeneration and promoting recovery of function in an array of neurodegenerative conditions.
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影响因子：
64.8
作者：
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通讯作者：
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