Oxidative metabolites in Alpha-Synucleinopathies

描述（由申请人提供）：氧化应激和炎症是与神经退行性疾病相关的确定因素，包括两种常见的α -突触核蛋白病：帕金森病（PD）和路易体痴呆（DLB）。PD和DLB的病理标志是含有神经元蛋白-突触核蛋白的称为路易体的细胞质聚集体。散发性因素占疾病病例的90%，已被证明可增加与α突触核蛋白聚集/发病机制有关的活性氧（ROS）水平。本研究的目的是确定ros氧化代谢物是否能在体外加速α -突触核蛋白聚集。体外结果的生物学相关性将通过评估氧化代谢物对表达α突触核蛋白的细胞的影响，以及通过量化病变脑组织中ros氧化代谢物的水平来解决。这些实验将探讨ros氧化代谢物在散发性α -突触核蛋白病中的可能作用。

DESCRIPTION (provided by applicant): Oxidative stress and inflammation are established factors associated with neurodegenerative diseases, including two common alpha-synucleinopathies: Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). The pathological hallmark of PD and DLB are cytoplasmic aggregates called Lewy bodies containing the neuronal protein alpha synuclein. Sporadic factors, which account for >90% of disease cases, have been shown to increase levels of reactive oxygen species (ROS) that are implicated in alpha synuclein aggregation/ pathogenesis. The goal of this research is to determine whether ROS-oxidized metabolites can accelerate alpha synuclein aggregation in vitro. The biological relevance of the in vitro results will be addressed by evaluating the effect of oxidative metabolites on cells expressing alpha synuclein, and by quantifying the levels of ROS-oxidized metabolites in diseased brain tissue. These experiments will address a possible role for ROS-oxidized metabolites in sporadic alpha-synucleinopathies.