Is LRRK2 the missing link between inflammatory bowel disease and Parkinson's disease?
Is LRRK2 the missing link between inflammatory bowel disease and Parkinson's disease?
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DOI：
10.1038/s41531-021-00170-1
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发表时间：
2021-03-09
期刊：
影响因子：
--
通讯作者：
Tansey MG
中科院分区：
文献类型：
--
作者：
Herrick MK;Tansey MG
帕金森病（PD）的发病机制和进展中涉及胃肠道系统的联系已变得越来越普遍。PD与克罗恩病（CD）有几个相似之处。肠道炎症在PD和CD中均很常见，并被假设为导致PD神经病理学。富含亮氨酸重复序列激酶2（LRRK 2）的突变是PD的最大遗传贡献者之一。LRRK 2的变异体也与CD发病率增加相关。自发现以来，LRRK 2一直在神经元中进行深入研究，尽管有多条证据表明LRRK 2在免疫细胞中高度表达。基于在CD患者的发炎结肠组织和散发性PD患者的外周免疫细胞中相对于匹配对照可检测到更高水平的LRRK 2的事实，我们证实LRRK 2调节炎症过程。因此，LRRK 2可能处于十字路口，由此肠道炎症和CD中较高的LRRK 2水平可能是散发性PD风险增加的生物标志物和/或可能代表增加PD风险的炎性疾病中易于处理的治疗靶点。在这里，我们将重点回顾PD和CD如何共享重叠的表型，特别是在免疫系统背景下的LRRK 2方面，这可能是未来治疗的目标。
Links that implicate the gastrointestinal system in Parkinson’s disease (PD) pathogenesis and progression have become increasingly common. PD shares several similarities with Crohn’s disease (CD). Intestinal inflammation is common in both PD and CD and is hypothesized to contribute to PD neuropathology. Mutations in leucine-rich repeat kinase 2 (LRRK2) are one of the greatest genetic contributors to PD. Variants in LRRK2 have also been associated with increased incidence of CD. Since its discovery, LRRK2 has been studied intensely in neurons, despite multiple lines of evidence showing that LRRK2 is highly expressed in immune cells. Based on the fact that higher levels of LRRK2 are detectable in inflamed colonic tissue from CD patients and in peripheral immune cells from sporadic PD patients relative to matched controls, we posit that LRRK2 regulates inflammatory processes. Therefore, LRRK2 may sit at a crossroads whereby gut inflammation and higher LRRK2 levels in CD may be a biomarker of increased risk for sporadic PD and/or may represent a tractable therapeutic target in inflammatory diseases that increase risk for PD. Here we will focus on reviewing how PD and CD share overlapping phenotypes, particularly in terms of LRRK2 in the context of the immune system, that could be targeted in future therapies.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
9.3
作者：
Eidson LN;Kannarkat GT;Barnum CJ;Chang J;Chung J;Caspell-Garcia C;Taylor P;Mollenhauer B;Schlossmacher MG;Ereshefsky L;Yen M;Kopil C;Frasier M;Marek K;Hertzberg VS;Tansey MG
通讯作者：
Tansey MG
DOI：
10.1038/s41531-017-0010-8
发表时间：
2017
期刊：
NPJ Parkinson's disease
影响因子：
--
作者：
Cook DA;Kannarkat GT;Cintron AF;Butkovich LM;Fraser KB;Chang J;Grigoryan N;Factor SA;West AB;Boss JM;Tansey MG
通讯作者：
Tansey MG
DOI：
10.9758/cpn.2018.16.4.422
发表时间：
2018-11-30
期刊：
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
影响因子：
--
作者：
Do J;Woo J
通讯作者：
Woo J
影响因子：
1.6
作者：
Chen L;Wang W;Zhou R;Ng SC;Li J;Huang M;Zhou F;Wang X;Shen B;A Kamm M;Wu K;Xia B
通讯作者：
Xia B