Bioanalytical and Biomarker, Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company, New York, NY 10016, USA.
Int J Mol Sci. 2022 Aug 18;23(16):9299. doi: 10.3390/ijms23169299.
Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics is an unbiased quantitative tool capable of the high throughput quantitation of thousands of proteins from minimal sample volumes. We review recent proteomic studies in human tissues, plasma, cerebrospinal fluid (CSF), and exosomes in ALS and PD that identify proteins with potential utility as biomarkers. Further, we review disease-related post-translational modifications in key proteins TDP43 in ALS and α-synuclein in PD studies, which may serve as biomarkers. We compare relative and absolute quantitative proteomic approaches in key biomarker studies in ALS and PD and discuss recent technological advancements which may identify suitable biomarkers for the early-diagnosis treatment efficacy of these diseases.
神经退行性疾病，如肌萎缩性侧索硬化症（ALS）和帕金森病（PD），其特征均为致病性蛋白聚集体与神经元进行性退化和行为功能丧失相关。这两种疾病都缺乏用于诊断和治疗效果评估的生物标志物。蛋白质组学是一种无偏的定量工具，能够从小体积样本中高通量定量数千种蛋白质。我们综述了最近在 ALS 和 PD 的人类组织、血浆、脑脊液（CSF）和外泌体中的蛋白质组学研究，这些研究鉴定了具有作为生物标志物潜在用途的蛋白质。此外，我们综述了 ALS 中 TDP43 和 PD 中α-突触核蛋白等关键蛋白的疾病相关翻译后修饰，它们可能作为生物标志物。我们比较了 ALS 和 PD 中关键生物标志物研究中的相对和绝对定量蛋白质组学方法，并讨论了最近的技术进展，这些进展可能为这些疾病的早期诊断和治疗效果评估确定合适的生物标志物。
