Scholarlink

<p>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<sub>6</sub> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月26日

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

摘要

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 B6 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.