Parkinson's disease-implicated kinases in the brain; insights into disease pathogenesis.
Parkinson's disease-implicated kinases in the brain; insights into disease pathogenesis.
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帕金森氏病在大脑中刺激的激酶；洞察疾病发病机理。
DOI：
10.3389/fnmol.2014.00057
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发表时间：
2014
影响因子：
4.8
通讯作者：
Halliday GM
中科院分区：
文献类型：
--
作者：
Dzamko N;Zhou J;Huang Y;Halliday GM
大量证据表明，蛋白激酶功能异常与帕金森氏病(PD)的病因有关。定义帕金森病的病理蛋白α-突触核蛋白的磷酸化水平升高，与其在神经元中的聚集和毒性积累有关，而PTEN诱导的假定激酶1和富含亮氨酸的重复蛋白2的基因错义突变增加了帕金森病的易感性。实验证据还将磷脂酰肌醇3-激酶和丝裂原活化蛋白激酶信号通路等信号通路与帕金森病联系起来。了解这些酶或其底物在脑组织中的水平或活性与病理状态的关系如何变化，可以为疾病的发病机制提供洞察力。此外，了解激酶功能障碍发生的时间和地点非常重要，因为对其中一些信号通路的调节可能会导致帕金森病的治疗。本文将对目前已知的这些PD相关的蛋白激酶在病理性人死后脑组织中的表达情况进行综述。
Substantial evidence implicates abnormal protein kinase function in various aspects of Parkinson’s disease (PD) etiology. Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis. Moreover, understanding when and where kinase dysfunction occurs is important as modulation of some of these signaling pathways can potentially lead to PD therapeutics. This review will summarize what is currently known in regard to the expression of these PD-implicated kinases in pathological human postmortem brain tissue.
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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：
6.1
作者：
Chu, Yaping;Dodiya, Hemraj;Kordower, Jeffrey H.
通讯作者：
Kordower, Jeffrey H.
影响因子：
--
作者：
Alvarez-Erviti, Lydia;Rodriguez-Oroz, Maria C.;Schapira, Anthony H. V.
通讯作者：
Schapira, Anthony H. V.
影响因子：
2.4
作者：
Biskup S;Moore DJ;Rea A;Lorenz-Deperieux B;Coombes CE;Dawson VL;Dawson TM;West AB
通讯作者：
West AB
影响因子：
3.7
作者：
Crews L;Spencer B;Desplats P;Patrick C;Paulino A;Rockenstein E;Hansen L;Adame A;Galasko D;Masliah E
通讯作者：
Masliah E