Mass spectrometry imaging: Linking neurodegeneration with environmental exposure

描述(申请人提供)：神经退行性疾病(ND)，如阿尔茨海默氏症、帕金森氏症和肌萎缩侧索硬化症，在遗传风险因素的背景下，与环境暴露于多种化学物质有关。然而，环境因素的确切作用和疾病标志物的建立仍然难以捉摸；特别是在疾病发生之前发生的早期标志物。对于帕金森氏症等ND疾病，氧化应激和线粒体功能障碍是已知的致病因素，而大脑中对神经元功能至关重要的富脂区域是敏感靶点，在疾病病因中发挥关键作用。局部的血脂浓度提供了 关于新城疫功能状态和分子病理生物学的重要信息。传统的分子生物学技术，如原位杂交和免疫组织化学，非常适合于表征mRNA和蛋白质的丰度，而质谱学成像(MSI)能够识别和定位组织中的单个脂质和代谢物，从而提供重要的补充信息。本项目致力于开发一个基于互补质谱学的平台，用于对组织中的脂质和代谢物进行高空间分辨率和高灵敏度的定量成像，以便在细胞水平上获得疾病早期的分子标志物。这一能力对于促进分子水平了解环境化学暴露对神经退化的影响至关重要。

DESCRIPTION (provided by applicant): Neurodegenerative diseases (ND) such as: Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis have been linked with environmental exposures to numerous chemicals within a background of genetic risk factors. However, the exact role of environmental agents and the establishment of markers of disease have remained elusive; particularly, early markers that occur prior to disease onset. For ND diseases such as Parkinson's, oxidative stress and mitochondrial dysfunction are known contributing factors and the lipid rich regions of the brain which are critical for neuronal functin are sensitive targets, playing a key role in disease etiology. Localized lipid concentrations offer important information on the functional state and molecular pathobiology of ND. Traditional molecular biology techniques, such as in situ hybridization and immunohistochemistry, are ideally suited for characterization of mRNA and protein abundances while mass spectrometry imaging (MSI) enables identification and spatial localization of individual lipids and metabolites in tissues thereby providing important complementary information. This project is focused on the development of a complementary mass spectrometry-based platform for quantitative imaging of lipids and metabolites in tissues with high spatial resolution and high sensitivity for obtaining molecular markers of the early disease stages at a cellular level. This capability is critical to advancing the molecular level understanding of the effect of environmental chemical exposure on neurodegeneration.