Toll-like receptor tolerance as a mechanism for neuroprotection.
Toll-like receptor tolerance as a mechanism for neuroprotection.
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DOI：
10.1007/s12975-010-0033-5
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发表时间：
2010-12-01
影响因子：
6.9
通讯作者：
Stenzel-Poore, Mary P.
中科院分区：
文献类型：
--
作者：
Vartanian, Keri B.;Stenzel-Poore, Mary P.
近年来研究发现，Toll样受体（TLRs）是脑卒中后组织损伤的重要介质。这一发现确定了一个新的目标，这对理解中风损伤的潜在机制和潜在的治疗方法至关重要。对TLR的大部分兴趣集中在它们的自我调节能力上--这一过程通常被称为“耐受性”，其中先前暴露于低水平TLR活化诱导了对随后的挑战的保护，否则会导致损伤。这一内源性过程已被用于中风的治疗。最近的研究表明，TLR途径可以通过预先暴露于TLR配体来重新编程，从而减少梗死面积并改善对缺血性损伤的神经学结果。对TLR重编程的分子机制的理解已经导致了TLR调控的多种途径的鉴定，包括靶向信号传导介质的抑制剂、转录后抑制基因的microRNA以及影响全局基因调控的染色质重塑中的表观遗传变化。在这篇综述中，我们讨论了TLR在介导脑卒中损伤中的作用，TLR预处理诱导TLR重编程的证据，以及TLR诱导的神经保护作用的可能机制。
It has been discovered recently that toll-like receptors (TLRs) are key mediators of tissue injury in response to stroke. This revelation has identified a new target critical to understanding the underlying mechanisms of stroke injury and potential therapies. Much of the interest in TLRs centers around their ability to self regulate – a process commonly referred to as “tolerance,” wherein prior exposure to low level TLR activation induces protection against a subsequent challenge that would otherwise cause damage. This endogenous process has been exploited in the setting of stroke. Recent studies show that TLR pathways can be reprogrammed via prior exposure to TLR ligands leading to decreased infarct size and improved neurological outcomes in response to ischemic injury. Efforts to understand the molecular mechanisms of TLR reprogramming have led to the identification of multiple routes of TLR regulation including inhibitors that target signaling mediators, microRNAs that suppress genes post-transcriptionally, and epigenetic changes in chromatin remodeling that affect global gene regulation. In this review, we discuss the role of TLRs in mediating injury due to stroke, evidence for TLR preconditioning-induced TLR reprogramming in response to stroke, and possible mechanisms of TLR-induced neuroprotection.
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影响因子：
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作者：
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通讯作者：
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DOI：
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