Peptide and Protein Biomarkers for Amyotrophic Lateral Sclerosis (ALS)

摘要/摘要 肌萎缩侧索硬化症(ALS)是运动神经元的最常见形式 退行性疾病，其特征是运动神经元进行性丧失 脊髓、脑干和大脑皮层。它可以袭击任何年龄的成年人， 虽然在50-55岁之间最常见。分子 导致这种疾病的机制尚不清楚，ALS的特异性生物标记物有 目前尚不清楚。我们的初步数据使用了基于质谱学的 蛋白质组学从脑脊液中鉴定出一组蛋白质生物标志物 在接近临床症状时诊断肌萎缩侧索硬化症的准确性很高 开始了。我们建议对更大范围的肌萎缩侧索硬化症和对照受试者进行研究 进一步验证和识别ALS的基于蛋白质的生物标记物。这样做的目的是 建议进一步探索肌萎缩侧索硬化症和对照组的脑脊液蛋白质组 鉴定肌萎缩侧索硬化症的多肽和/或蛋白质生物标志物。我们将利用液体 大屏幕无偏多肽的色谱-质谱学研究 区分肌萎缩侧索硬化症和对照受试者。然后，我们将验证我们的发现 分离受试者组并生成基于质谱学的方法以 量化脑脊液和/或血浆中区分肌萎缩侧索硬化症 控制受试者。然后我们将使用这组生物标志物来区分亚 ALS患者的人口，基于发病地点、年龄、性别或 疾病的发展。这些研究将为ALS产生新的生物标记物 可用于未来对ALS的诊断，并测试其监控能力 临床试验中的疾病进展或药物疗效。

Summary/Abstract Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron degenerative disease and is characterized by a progressive loss of motor neurons in the spinal cord, brain stem and cerebral cortex. It can strike adults of any age, though is most common between the ages of 50-55 years. The molecular mechanisms that cause this disease are unclear and biomarkers specific for ALS are currently unknown. Our preliminary data using mass spectrometry based proteomics identified a panel of protein biomarkers from cerebrospinal fluid (CSF) with a high level of accuracy for diagnosing ALS near the time of clinical symptom onset. We propose to examine a much larger group of ALS and control subjects to further validate and identify protein based biomarkers for ALS. The goals of this proposal are to further explore the CSF proteome of ALS and control subjects to identify peptide and/or protein biomarkers for ALS. We will utilize liquid chromatography based mass spectrometry in a large unbiased screen for peptides that distinguish ALS from control subjects. We will then validate our findings in separate subject groups and generate a mass spectrometry based method to quantify specific peptides within the CSF and/or plasma that distinguish ALS from control subjects. We will then use this panel of biomarkers to distinguish sub- populations of ALS patients based on site of disease onset, age, gender, or rate of disease progression. These studies will generate novel biomarkers for ALS that could be used in future diagnostics for ALS and tested for their ability to monitor disease progression or drug efficacy in clinical trials.