帕金森病的特征是维生素B6依赖的炎症性犬尿氨酸途径功能障碍。

Parkinson's disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction.

作者信息

Wilson Edward N, Umans Jacob, Swarovski Michelle S, Minhas Paras S, Mendiola Justin H, Midttun Øivind, Ulvik Arve, Shahid-Besanti Marian, Linortner Patricia, Mhatre Siddhita D, Wang Qian, Channappa Divya, Corso Nicole K, Tian Lu, Fredericks Carolyn A, Kerchner Geoffrey A, Plowey Edward D, Cholerton Brenna, Ueland Per M, Zabetian Cyrus P, Gray Nora E, Quinn Joseph F, Montine Thomas J, Sha Sharon J, Longo Frank M, Wolk David A, Chen-Plotkin Alice, Henderson Victor W, Wyss-Coray Tony, Wagner Anthony D, Mormino Elizabeth C, Aghaeepour Nima, Poston Kathleen L, Andreasson Katrin I

机构信息

Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA.

Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.

出版信息

NPJ Parkinsons Dis. 2025 Apr 26;11(1):96. doi: 10.1038/s41531-025-00964-7.

DOI:10.1038/s41531-025-00964-7

PMID:40287426

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12033312/

Abstract

Recent studies demonstrate that Parkinson's disease (PD) is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). Here, we used mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. We found increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B deficiency. Furthermore, increased QA tracked with CSF tau, CSF soluble TREM2 (sTREM2) and severity of both motor and non-motor PD clinical symptoms. Finally, PD patient subgroups with distinct KP profiles displayed distinct PD clinical features. These data validate the KP as a site of brain and periphery crosstalk, integrating B-vitamin status, inflammation and metabolism to ultimately influence PD clinical manifestation.

摘要

最近的研究表明，帕金森病（PD）与通过犬尿氨酸途径（KP）的代谢通量失调有关，在该途径中，色氨酸转化为犬尿氨酸（KYN），随后KYN被代谢为神经活性化合物喹啉酸（QA）和犬尿喹啉酸（KA）。在此，我们使用质谱法比较了158名未受损的老年人和177名PD参与者的血液和脑脊液（CSF）中的KP代谢物。我们发现，PD参与者的血浆和CSF中神经兴奋性QA/KA比值升高，这与外周和脑部炎症以及维生素B缺乏有关。此外，QA升高与CSF tau、CSF可溶性触发受体表达量2（sTREM2）以及运动和非运动PD临床症状的严重程度相关。最后，具有不同KP谱的PD患者亚组表现出不同的PD临床特征。这些数据证实了KP是大脑与外周相互作用的部位，整合了B族维生素状态、炎症和代谢，最终影响PD的临床表现。