LRRK2 Pathways Leading to Neurodegeneration.
LRRK2 Pathways Leading to Neurodegeneration.
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DOI：
10.1007/s11910-015-0564-y
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发表时间：
2015-07
影响因子：
5.6
通讯作者：
Cookson MR
中科院分区：
文献类型：
--
作者：
Cookson MR
LRRK2突变与许多家族中的遗传性帕金森病（PD）相关，并且含有LRRK2基因的遗传位点含有散发性PD的危险因素。LRRK2蛋白含有几个结构域，表明在细胞信号传导中的作用，包括激酶结构域。同样清楚的是，LRRK2在物理上或遗传上与其他几种与PD有关的重要蛋白质相互作用，这表明LRRK2可能是帕金森综合征基础通路的核心参与者。因此，LRRK2被认为是治疗干预的合理靶点，激酶抑制是最积极的追求。然而，LRRK2生物学和功能的几个基本方面目前仍未解决。这篇综述将集中在LRRK2的正常功能的关键问题，以及这可能是如何与PD的病理生理。
Mutations in LRRK2 are associated with inherited Parkinson’s disease (PD) in a large number of families, and the genetic locus containing the LRRK2 gene contains a risk factor for sporadic PD. The LRRK2 protein contains several domains that suggest a role in cellular signaling, including a kinase domain. It is also clear that LRRK2 interacts, either physically or genetically, with several other important proteins implicated in PD, suggesting that LRRK2 may be a central player in the pathways that underlie parkinsonism. As such, LRRK2 has been proposed to be a plausible target for therapeutic intervention, with kinase inhibition being pursued most actively. However, there are still several fundamental aspects of LRRK2 biology and function that remain unresolved at this time. This review will focus on the key questions of normal function of LRRK2 and how this might be related to the path-ophysiology of PD.
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DOI：
10.1093/brain/awt315
发表时间：
2014-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Foley AR;Menezes MP;Pandraud A;Gonzalez MA;Al-Odaib A;Abrams AJ;Sugano K;Yonezawa A;Manzur AY;Burns J;Hughes I;McCullagh BG;Jungbluth H;Lim MJ;Lin JP;Megarbane A;Urtizberea JA;Shah AH;Antony J;Webster R;Broomfield A;Ng J;Mathew AA;O'Byrne JJ;Forman E;Scoto M;Prasad M;O'Brien K;Olpin S;Oppenheim M;Hargreaves I;Land JM;Wang MX;Carpenter K;Horvath R;Straub V;Lek M;Gold W;Farrell MO;Brandner S;Phadke R;Matsubara K;McGarvey ML;Scherer SS;Baxter PS;King MD;Clayton P;Rahman S;Reilly MM;Ouvrier RA;Christodoulou J;Züchner S;Muntoni F;Houlden H
通讯作者：
Houlden H
影响因子：
4.5
作者：
Do CB;Tung JY;Dorfman E;Kiefer AK;Drabant EM;Francke U;Mountain JL;Goldman SM;Tanner CM;Langston JW;Wojcicki A;Eriksson N
通讯作者：
Eriksson N
影响因子：
3.7
作者：
Fenner BJ;Scannell M;Prehn JH
通讯作者：
Prehn JH
DOI：
10.1073/pnas.1318306111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Beilina, Alexandria;Rudenko, Iakov N.;Cookson, Mark R.
通讯作者：
Cookson, Mark R.
影响因子：
11.2
作者：
Al-Mulla, Fahd;Bitar, Milad S.;Kolch, Walter
通讯作者：
Kolch, Walter