Modeling the simultaneous dynamics of proteins in blood plasma and the cerebrospinal fluid in human in vivo

The analysis of protein dynamics or turnover in patients has the potential to reveal altered protein recycling such as in Alzheimer disease, and to provide informative data regarding drug efficacy, or certain biological processes. The observed protein dynamics in a solid tissue or a fluid is the net result of protein synthesis and degradation, but also transport across biological compartments. We report a first model to simultaneously model protein dynamics observed in blood plasma and the cerebrospinal fluid (CSF) taking into account transport. We applied this model to 65 proteins of a single individual displaying similar or very different dynamics in plasma and CSF. The model structure indicates an active control at the blood-CSF barrier. This type of model has the potential to reveal altered transport or barriers resulting from disease in future studies.

对患者体内蛋白质动力学（protein dynamics）或更新周转的分析，有望揭示阿尔茨海默病（Alzheimer disease）等疾病中发生改变的蛋白质循环过程，并为药物疗效或特定生物学过程提供具有重要参考价值的研究数据。在实体组织或体液中观测到的蛋白质动力学，是蛋白质合成、降解以及跨生物区室（biological compartments）转运共同作用的净结果。本研究首次提出一种可同时建模血浆（blood plasma）与脑脊液（cerebrospinal fluid，CSF）中观测到的蛋白质动力学的模型，该模型考量了跨区室转运过程。我们将该模型应用于某一个体的65种蛋白质，这些蛋白质在血浆与脑脊液中的动力学特征呈现相似或显著差异。该模型的结构表明，血脑脊液屏障（blood-CSF barrier）存在主动调控机制。此类模型有望在未来的研究中揭示疾病引发的转运过程或屏障功能异常。