Parkinson's disease and immune system: is the culprit LRRKing in the periphery?

Parkinson's disease and immune system: is the culprit LRRKing in the periphery?
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DOI:
10.1186/1742-2094-9-94
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发表时间:
2012-07-09
影响因子:
9.3
通讯作者:
Bubacco L
Bubacco L
中科院分区:
医学1区
文献类型:
--
作者:
Greggio E;Civiero L;Bisaglia M;Bubacco L

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富含亮氨酸的重复蛋白激酶2(LRRK2)是一种大的多结构域激酶/GTP酶,最近被认为与三种病理疾病有关:帕金森氏病、克罗恩病和麻风。虽然LRRK2的生理功能尚不清楚,但它在免疫细胞和组织中的高表达,它被干扰素γ上调,以及它作为免疫反应转录因子NFAT1的负调节因子的功能,表明它在炎症反应中具有潜在的作用。在这篇综述中,我们讨论了关于LRRK2如何在炎症反应中发挥作用的最新发现,并提出了一种情景,即由帕金森氏病LRRK2突变介导的有害影响可能起始于外周并延伸到中枢神经系统,结果是促炎症因子水平增加,渗透到血脑屏障。
Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain kinase/GTPase that has been recently linked to three pathological conditions: Parkinson’s disease; Crohn’s disease; and leprosy. Although LRRK2 physiological function is poorly understood, a potential role in inflammatory response is suggested by its high expression in immune cells and tissues, its up-regulation by interferon γ, and its function as negative regulator of the immune response transcription factor NFAT1. In this review we discuss the most recent findings regarding how LRRK2 could be a player in the inflammatory response and we propose a scenario where the detrimental effects mediated by Parkinson’s disease LRRK2 mutations may initiate in the periphery and extend to the central nervous system as a consequence of increased levels of pro-inflammatory factors permeable to the blood brain barrier.
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