蛋白质组
生物标志物
疾病
生物标志物发现
计算生物学
帕金森病
生物
蛋白质组学
生物信息学
医学
生物化学
病理
基因
作者
Marie‐Therese Mackmull,Luise Nagel,Fabian Sesterhenn,Jan Muntel,Jan Großbach,Patrick Stalder,Roland Bruderer,Lukas Reiter,Wilma D. J. van de Berg,Natalie de Souza,Andreas Beyer,Paola Picotti
标识
DOI:10.1038/s41594-022-00837-0
摘要
Parkinson’s disease (PD) is a prevalent neurodegenerative disease for which robust biomarkers are needed. Because protein structure reflects function, we tested whether global, in situ analysis of protein structural changes provides insight into PD pathophysiology and could inform a new concept of structural disease biomarkers. Using limited proteolysis–mass spectrometry (LiP–MS), we identified 76 structurally altered proteins in cerebrospinal fluid (CSF) of individuals with PD relative to healthy donors. These proteins were enriched in processes misregulated in PD, and some proteins also showed structural changes in PD brain samples. CSF protein structural information outperformed abundance information in discriminating between healthy participants and those with PD and improved the discriminatory performance of CSF measures of the hallmark PD protein α-synuclein. We also present the first analysis of inter-individual variability of a structural proteome in healthy individuals, identifying biophysical features of variable protein regions. Although independent validation is needed, our data suggest that global analyses of the human structural proteome will guide the development of novel structural biomarkers of disease and enable hypothesis generation about underlying disease processes.
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