Liu Guoxiang, Aliaga Leonardo, Cai Huaibin
Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Future Neurol. 2012 Mar;7(2):145-153. doi: 10.2217/fnl.12.2.
Of the various genetic factors contributing to the pathogenesis of Parkinson's disease (PD), only mutations in α-synuclein (α-syn) and LRRK2 genes cause clinical and neuropathological phenotypes closely resembling the sporadic cases. Therefore, studying the pathophysiological functions of these two PD-related genes is particularly informative in understanding the underlying molecular pathogenic mechanism of the disease. PD-related missense and multiplication mutations in α-syn may cause both early- and late-onset PD, whereas various PD-related LRRK2 missense mutations may contribute to the more common late-onset PD. While intensive studies have been carried out to elucidate the pathogenic properties of PD-related mutant α-syn and LRRK2, our knowledge of their normal functions and their potential genetic interplay remains rudimental. In this review, we summarize the progress made regarding the pathophysiological functions of α-syn, LRRK2 and their interaction in PD, based on the available literature and our unpublished observations.
在导致帕金森病（PD）发病机制的各种遗传因素中，只有α-突触核蛋白（α-syn）和富含亮氨酸重复激酶2（LRRK2）基因的突变会导致临床和神经病理表型，与散发性病例极为相似。因此，研究这两个与PD相关基因的病理生理功能，对于理解该疾病潜在的分子致病机制具有特别重要的意义。α-syn中与PD相关的错义突变和倍增突变可能导致早发性和晚发性PD，而各种与PD相关的LRRK2错义突变可能导致更为常见的晚发性PD。尽管已经开展了大量研究来阐明与PD相关的突变型α-syn和LRRK2的致病特性，但我们对它们的正常功能及其潜在的基因相互作用的了解仍然十分有限。在这篇综述中，我们基于现有文献和我们未发表的观察结果，总结了α-syn、LRRK2的病理生理功能及其在PD中的相互作用方面所取得的进展。
