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既定因素，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的病理标志是细胞质聚集体，称为路易体，含有神经元蛋白α突触核蛋白。占>90%的疾病病例的散发性因素已显示增加与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氧化代谢产物是否可以在体外加速α突触核蛋白聚集。将通过评价氧化代谢产物对表达α突触核蛋白的细胞的影响，并通过定量患病脑组织中ROS氧化代谢产物的水平，来解决体外结果的生物学相关性。这些实验将解决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.