Sonninen Tuuli-Maria, Peltonen Sanni, Niskanen Jonna, Hämäläinen Riikka H, Koistinaho Jari, Lehtonen Šárka
A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland.
Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland.
Int J Mol Sci. 2024 Nov 29;25(23):12874. doi: 10.3390/ijms252312874.
The blood-brain barrier (BBB) serves as an interface between the bloodstream and the central nervous system. It limits the movement of molecules and immune cells, regulates the entry of nutrients, and removes waste products from the brain. The dysfunction of the BBB has been identified in Parkinson's disease (PD) but the role of the BBB and endothelial cells (ECs) has not been well studied. G2019S mutation is the most common PD causing mutation with similar pathophysiology than in sporadic cases. How the mutation affects EC function has not been investigated previously in patient cells. In the study, we used iPSC-derived ECs from PD patients with the mutation as well as cells from healthy individuals. We report that PD patients' ECs have higher levels of α-synuclein and an decreased maximal and ATP-linked respiration and altered response to inflammatory exposure, especially to TNFα. In addition, transcriptomic analysis showed upregulation of fatty-acid-synthesis-related pathways in PD patients' ECs and the downregulation of lncRNA , both of which have been associated with PD. Altogether, PD patients' ECs manifest some of the PD-related hallmarks and are likely to contribute to the pathogenesis of PD.
血脑屏障（BBB）是血液与中枢神经系统之间的界面。它限制分子和免疫细胞的移动，调节营养物质的进入，并清除大脑中的废物。帕金森病（PD）中已发现血脑屏障功能障碍，但血脑屏障和内皮细胞（ECs）的作用尚未得到充分研究。G2019S突变是导致帕金森病最常见的突变，其病理生理学与散发性病例相似。此前尚未在患者细胞中研究该突变如何影响内皮细胞功能。在这项研究中，我们使用了来自携带该突变的帕金森病患者的诱导多能干细胞衍生的内皮细胞以及健康个体的细胞。我们报告称，帕金森病患者的内皮细胞中α-突触核蛋白水平较高，最大呼吸和ATP相关呼吸降低，对炎症暴露，尤其是对肿瘤坏死因子α（TNFα）的反应改变。此外，转录组分析显示帕金森病患者内皮细胞中脂肪酸合成相关途径上调，长链非编码RNA下调，这两者均与帕金森病有关。总之，帕金森病患者的内皮细胞表现出一些与帕金森病相关的特征，可能有助于帕金森病的发病机制。
