School of Medical Sciences, University of New South Wales Kensington, NSW, Australia ; Neuroscience Research Australia Randwick, NSW, Australia.
Front Mol Neurosci. 2014 Jun 24;7:57. doi: 10.3389/fnmol.2014.00057. eCollection 2014.
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.
大量证据表明，异常的蛋白激酶功能与帕金森病（PD）发病机制的各个方面有关。PD 定义性病理蛋白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相关，而 PTEN 诱导的假定激酶 1 和富含亮氨酸重复激酶 2 中的激酶的遗传错义突变会增加 PD 的易感性。实验证据还将磷酸肌醇 3-激酶和丝裂原活化蛋白激酶等信号通路的激酶与 PD 联系起来。了解这些酶或其底物的水平或活性在与病理状态相关的脑组织中如何变化，可以深入了解疾病的发病机制。此外，了解激酶功能障碍发生的时间和地点很重要，因为这些信号通路的某些调节可能会导致 PD 治疗药物的出现。本文将综述目前已知的与病理状态下人类尸检脑组织中这些 PD 相关激酶的表达有关的内容。
