Cardona Fernando, Perez-Tur Jordi
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC). Calle Jaime Roig 11, Valencia E46010, Spain.
Curr Protein Pept Sci. 2017;18(7):765-778. doi: 10.2174/1389203717666160311122152.
In order to explain the molecular causes of Parkinson's Disease (PD) it is important to understand the effect that mutations described as causative of the disease have at the functional level. In this special issue, several authors have been reviewing the effects in PD and other parkinsonisms of mutations described in LRRK2, α-synuclein, PINK1-Parkin-DJ-1, UCHL1, ATP13A2, GBA, VPS35, FBOX7 and HTRA2. In this review, we compile the knowledge about other proteins with a more general role in neurodegenerative diseases (MAPT) or for which less data is available due to its recent discovery (EIF4G1, DNAJC13), the lack of structural or functional data (as for PLA2G6 or DNAJC6), or even their doubtful association with the disease (as for GIGYF2, SYNJ1 and SPR). Also the cellular pathways involved in this disease are reviewed, with the goal of having an overview of the effects on the proteins and its possible role in the disease. This knowledge could also serve as the basis for designing tools that may potentially be used as a treatment for the disease, such as inhibitory or activating molecules, as well as other involved in regulating the half-life of the proteins involved.
为了解释帕金森病（PD）的分子病因，重要的是要了解被描述为该疾病病因的突变在功能水平上所产生的影响。在本期特刊中，几位作者回顾了LRRK2、α-突触核蛋白、PINK1-Parkin-DJ-1、UCHL1、ATP13A2、GBA、VPS35、FBOX7和HTRA2中所描述的突变在PD和其他帕金森综合征中的影响。在这篇综述中，我们汇总了关于在神经退行性疾病中具有更广泛作用的其他蛋白质（MAPT）的知识，或者由于其最近才被发现（EIF4G1、DNAJC13）、缺乏结构或功能数据（如PLA2G6或DNAJC6），甚至它们与该疾病的关联存疑（如GIGYF2、SYNJ1和SPR）而数据较少的蛋白质的知识。此外，还对该疾病所涉及的细胞途径进行了综述，目的是全面了解这些蛋白质所受的影响及其在疾病中的可能作用。这些知识也可为设计可能用作该疾病治疗手段的工具提供基础，如抑制性或激活分子，以及其他参与调节相关蛋白质半衰期的分子。
