Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease
Abstract We previously demonstrated that kynurenine pathway (KP) dysregulation associates with Parkinson’s disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n = 202 (116 PD (“OFF”), 86 controls); CSF: n = 183 (108, 75). Consistent with pr...
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Nature Portfolio
2025-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-00949-6 |
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| author | Leslie C. Jellen Martha L. Escobar Galvis Qiong Sha Christine Isaguirre Amy Johnson Zach Madaj Mechelle M. Lewis Ryan D. Sheldon Lan Kong Xuemei Huang Lena Brundin |
| author_facet | Leslie C. Jellen Martha L. Escobar Galvis Qiong Sha Christine Isaguirre Amy Johnson Zach Madaj Mechelle M. Lewis Ryan D. Sheldon Lan Kong Xuemei Huang Lena Brundin |
| author_sort | Leslie C. Jellen |
| collection | DOAJ |
| description | Abstract We previously demonstrated that kynurenine pathway (KP) dysregulation associates with Parkinson’s disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n = 202 (116 PD (“OFF”), 86 controls); CSF: n = 183 (108, 75). Consistent with previous findings, we detected significantly higher concentrations of neurotoxic 3-hydroxykynurenine in plasma and lower concentrations of neuroprotective kynurenic acid along with higher neurotoxic quinolinic acid/kynurenic acid ratios in CSF of PD patients. Additionally, 10 markers showed sex-based differences, with more pronounced dysregulation in females. These 10 markers loaded to a single principal component linked to higher UPDRS I and II scores. Together, this suggests a composite signature of KP dysregulation in PD that is associated with worse symptoms and more prevalent in women. This work shows that KP dysregulation in peripheral and central compartments is linked to symptom severity in PD and warrants further systematic studies unraveling sex-dependent metabolic differences. |
| format | Article |
| id | doaj-art-dbbe85db27d341bc83a9f2bb75d88301 |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-dbbe85db27d341bc83a9f2bb75d883012025-08-20T03:09:34ZengNature Portfolionpj Parkinson's Disease2373-80572025-05-0111111210.1038/s41531-025-00949-6Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s diseaseLeslie C. Jellen0Martha L. Escobar Galvis1Qiong Sha2Christine Isaguirre3Amy Johnson4Zach Madaj5Mechelle M. Lewis6Ryan D. Sheldon7Lan Kong8Xuemei Huang9Lena Brundin10Department of Neurology, Translational Brain Research Center, Penn State University-Milton S. Hershey Medical CenterOffice of the Cores, Van Andel InstituteDepartment of Neurodegenerative Science, Van Andel InstituteMass Spectrometry Core, Van Andel InstituteMass Spectrometry Core, Van Andel InstituteBioinformatics and Biostatistics Core, Van Andel InstituteDepartment of Neurology, Translational Brain Research Center, Penn State University-Milton S. Hershey Medical CenterMass Spectrometry Core, Van Andel InstitutePublic Health Sciences, Penn State University-Milton S. Hershey Medical CenterDepartment of Neurology, Translational Brain Research Center, Penn State University-Milton S. Hershey Medical CenterDepartment of Neurodegenerative Science, Van Andel InstituteAbstract We previously demonstrated that kynurenine pathway (KP) dysregulation associates with Parkinson’s disease (PD) and its symptoms. Here, we profiled 16 KP-related markers in a second, independent cohort; plasma: n = 202 (116 PD (“OFF”), 86 controls); CSF: n = 183 (108, 75). Consistent with previous findings, we detected significantly higher concentrations of neurotoxic 3-hydroxykynurenine in plasma and lower concentrations of neuroprotective kynurenic acid along with higher neurotoxic quinolinic acid/kynurenic acid ratios in CSF of PD patients. Additionally, 10 markers showed sex-based differences, with more pronounced dysregulation in females. These 10 markers loaded to a single principal component linked to higher UPDRS I and II scores. Together, this suggests a composite signature of KP dysregulation in PD that is associated with worse symptoms and more prevalent in women. This work shows that KP dysregulation in peripheral and central compartments is linked to symptom severity in PD and warrants further systematic studies unraveling sex-dependent metabolic differences.https://doi.org/10.1038/s41531-025-00949-6 |
| spellingShingle | Leslie C. Jellen Martha L. Escobar Galvis Qiong Sha Christine Isaguirre Amy Johnson Zach Madaj Mechelle M. Lewis Ryan D. Sheldon Lan Kong Xuemei Huang Lena Brundin Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease npj Parkinson's Disease |
| title | Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease |
| title_full | Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease |
| title_fullStr | Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease |
| title_full_unstemmed | Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease |
| title_short | Sex differences in peripheral and central dysregulation of the kynurenine pathway in Parkinson’s disease |
| title_sort | sex differences in peripheral and central dysregulation of the kynurenine pathway in parkinson s disease |
| url | https://doi.org/10.1038/s41531-025-00949-6 |
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