Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Chair and Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Curr Genomics. 2013 Dec;14(8):502-17. doi: 10.2174/1389202914666131210205839.
Although Parkinson's disease (PD) was first described almost 200 years ago, it remains an incurable disease with a cause that is not fully understood. Nowadays it is known that disturbances in the structure of pathological proteins in PD can be caused by more than environmental and genetic factors. Despite numerous debates and controversies in the literature about the role of mutations in the SNCA and PRKN genes in the pathogenesis of PD, it is evident that these genes play a key role in maintaining dopamine (DA) neuronal homeostasis and that the dysfunction of this homeostasis is relevant to both familial (FPD) and sporadic (SPD) PD with different onset. In recent years, the importance of alphasynuclein (ASN) in the process of neurodegeneration and neuroprotective function of the Parkin is becoming better understood. Moreover, there have been an increasing number of recent reports indicating the importance of the interaction between these proteins and their encoding genes. Among others interactions, it is suggested that even heterozygous substitution in the PRKN gene in the presence of the variants +2/+2 or +2/+3 of NACP-Rep1 in the SNCA promoter, may increase the risk of PD manifestation, which is probably due to ineffective elimination of over-expressed ASN by the mutated Parkin protein. Finally, it seems that genetic testing may be an important part of diagnostics in patients with PD and may improve the prognostic process in the course of PD. However, only full knowledge of the mechanism of the interaction between the genes associated with the pathogenesis of PD is likely to help explain the currently unknown pathways of selective damage to dopaminergic neurons in the course of PD.
虽然帕金森病（PD）在近 200 年前首次被描述，但它仍然是一种无法治愈的疾病，其病因尚未完全了解。如今，人们已经知道，PD 中病理性蛋白质结构的紊乱可能不仅由环境和遗传因素引起。尽管文献中关于 SNCA 和 PRKN 基因中的突变在 PD 发病机制中的作用存在许多争论和争议，但很明显，这些基因在维持多巴胺（DA）神经元内稳态方面起着关键作用，而这种内稳态的功能障碍与家族性（FPD）和散发性（SPD）PD 都有关，且具有不同的发病时间。近年来，α-突触核蛋白（ASN）在神经退行性过程中的重要性以及 Parkin 的神经保护功能正变得越来越清楚。此外，越来越多的最近报告表明这些蛋白质及其编码基因之间的相互作用非常重要。除其他相互作用外，有人认为，即使在 SNCA 启动子中存在 NACP-Rep1 的+2/+2 或+2/+3 变体的情况下，PRKN 基因中的杂合取代也可能增加 PD 表现的风险，这可能是由于突变 Parkin 蛋白无法有效消除过度表达的 ASN。最后，似乎遗传测试可能是 PD 患者诊断的重要组成部分，并且可以改善 PD 病程中的预后过程。然而，只有充分了解与 PD 发病机制相关的基因之间的相互作用机制，才有可能帮助解释 PD 过程中多巴胺能神经元选择性损伤的目前未知途径。
