ArticleScientific reports2019
The levels of the NMDA receptor co-agonist D-serine are reduced in the substantia nigra of MPTP-lesioned macaques and in the cerebrospinal fluid of Parkinson's disease patients.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Safety and efficacy of AST-001 in children with autism spectrum disorder: a 52-week multicenter long-term follow-up study.Frontiers in psychiatry · 2026Trial
- Novel Detection and Restorative Levodopa Treatment for Preclinical Diabetic Retinopathy.Diabetes · 2020Trial
- Ultra-performance liquid chromatography-mass spectrometry analysis of post-mortem brain tissue reveals specific amino acid profile dysregulation in Parkinson's disease and Alzheimer's disease patients.NPJ Parkinson's disease · 2026Article
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- PHGDH-mediated serine synthesis in astrocytes supports neuroinflammation by sustaining NADH level to promote histone acetylation.Cell death & disease · 2025Article
- SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- Future Perspectives of NMDAR in CNS Disorders.Molecules (Basel, Switzerland) · 2025Review
- Astrocytes Lingering at a Crossroads: Neuroprotection and Neurodegeneration in Neurocognitive Dysfunction.International journal of biological sciences · 2025Review
- The gut-brain axis: potential reshaping the future of anti-NMDAR encephalitis treatment.Frontiers in immunology · 2025Review
- Targeted Chiral Metabolomics of D-Amino Acids: Their Emerging Role as Potential Biomarkers in Neurological Diseases with a Focus on Their Liquid Chromatography-Mass Spectrometry Analysis upon Chiral Derivatization.International journal of molecular sciences · 2024Review
- Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.Molecular pharmacology · 2024Article
- Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.Translational psychiatry · 2024Article
- CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids.Analytical chemistry · 2023Article
- Changes in aspartate metabolism in the medial-prefrontal cortex of nicotine addicts based on J-edited magnetic resonance spectroscopy.Human brain mapping · 2023Article
- Perturbation of serine enantiomers homeostasis in the striatum of MPTP-lesioned monkeys and mice reflects the extent of dopaminergic midbrain degeneration.Neurobiology of disease · 2023Article
- L-serine: Neurological Implications and Therapeutic Potential.Biomedicines · 2023Review
- Detection and analysis of chiral molecules as disease biomarkers.Nature reviews. Chemistry · 2023Review
- D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans.Translational psychiatry · 2022Article
- Machine Learning algorithm unveils glutamatergic alterations in the post-mortem schizophrenia brain.Schizophrenia (Heidelberg, Germany) · 2022Article
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Authors and funding
18 authors at 9 institutions in 5 countries.
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Abstract
Dysfunction of NMDA receptor (NMDAR)-mediated transmission is supposed to contribute to the motor and non-motor symptoms of Parkinson's Disease (PD), and to L-DOPA-induced dyskinesia. Besides the main agonist L-glutamate, two other amino acids in the atypical D-configuration, D-serine and D-aspartate, activate NMDARs. In the present work, we investigated the effect of dopamine depletion on D-amino acids metabolism in the brain of MPTP-lesioned Macaca mulatta, and in the serum and cerebrospinal fluid of PD patients. We found that MPTP treatment increases D-aspartate and D-serine in the monkey putamen while L-DOPA rescues both D-amino acids levels. Conversely, dopaminergic denervation is associated with selective D-serine reduction in the substantia nigra. Such decrease suggests that the beneficial effect of D-serine adjuvant therapy previously reported in PD patients may derive from the normalization of endogenous D-serine levels and consequent improvement of nigrostriatal hypoglutamatergic transmission at glycine binding site. We also found reduced D-serine concentration in the cerebrospinal fluid of L-DOPA-free PD patients. These results further confirm the existence of deep interaction between dopaminergic and glutamatergic neurotransmission in PD and disclose a possible direct influence of D-amino acids variations in the changes of NMDAR transmission occurring under dopamine denervation and L-DOPA therapy.
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