Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan.
Biochem Biophys Res Commun. 2014 Sep 19;452(2):226-35. doi: 10.1016/j.bbrc.2014.06.028. Epub 2014 Jun 17.
Research on Parkinson's disease (PD) has made remarkable progress in recent decades, due largely to new genomic technologies, such as high throughput sequencing and microarray analyses. Since the discovery of a linkage of a missense mutation of the α-synuclein (αS) gene to a rare familial dominant form of PD in 1996, positional cloning and characterization of a number of familial PD risk factors have established a hypothesis that aggregation of αS may play a major role in the pathogenesis of PD. Furthermore, dozens of sensitizing alleles related to the disease have been identified by genome wide association studies (GWAS) and meta-GWAS, contributing to a better understanding of the pathological mechanisms of sporadic PD. Thus, the knowledge obtained from the association studies will be valuable for "the personal genome" of PD. Besides summarizing such progress, this paper focuses on the role of microRNAs in the field of PD research, since microRNAs might be promising as a biomarker and as a therapeutic reagent for PD. We further refer to a recent view that neurodegenerative diseases, including PD, coexist with metabolic disorders and are stimulated by type II diabetes, the most common disease among elderly populations. The development of genomic approaches may potentially contribute to therapeutic intervention for PD.
帕金森病(PD)的研究在近几十年来取得了显著的进展,这主要归功于新的基因组技术,如高通量测序和微阵列分析。自 1996 年发现α-突触核蛋白(αS)基因的一个错义突变与一种罕见的家族性显性形式的 PD 有关联以来,许多家族性 PD 风险因素的定位克隆和特征分析已经建立了一个假说,即αS 的聚集可能在 PD 的发病机制中起主要作用。此外,通过全基因组关联研究(GWAS)和元 GWAS 已经鉴定出数十种与疾病相关的敏感等位基因,这有助于更好地理解散发性 PD 的病理机制。因此,从关联研究中获得的知识对于 PD 的“个人基因组”将是有价值的。本文除了总结这些进展外,还重点介绍了 microRNAs 在 PD 研究领域的作用,因为 microRNAs 可能是一种有前途的 PD 生物标志物和治疗试剂。我们进一步提到了一个最近的观点,即包括 PD 在内的神经退行性疾病与代谢紊乱共存,并受到最常见于老年人群的 II 型糖尿病的刺激。基因组方法的发展可能有助于 PD 的治疗干预。