ArticleCell reports2016
Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 75 citations in OpenAlex.
- [New interdisciplinary S3 guidelines on deletion syndrome 22q11.2, a genetic disease predisposing to neuropsychiatric morbidity].Der Nervenarzt · 2026Review
- Transcriptional profiling reveals brain region-specific changes in gene expression induced by chronic unpredictable mild stress between stress-susceptible and stress-resilient mice.Psychopharmacology · 2026Article
- EEG power spectral and microstate analyses in the 22q11.2 deletion syndrome: from genetic risk to schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Serum metabolomic profiles associated with psychoneurological symptoms in women with early-stage breast cancer over one year.Frontiers in oncology · 2026Article
- Gut microbiota and brain aging: a comparative review of African and western populations.Frontiers in aging neuroscience · 2026Review
- Cntn4 Gene Deficiency Promotes Autism-Like Phenotypes Associated with Gut Microbiota Perturbations and Gut-Brain Axis Metabolomic Alterations in Mice.Molecular neurobiology · 2025Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Sideroflexins enable mitochondrial transport of polar neutral amino acids.bioRxiv : the preprint server for biology · 2025Article
- Variations in salivary microbiota and metabolic phenotype related to oral lichen planus with psychiatric symptoms.BMC oral health · 2025Article
- Neurological Insights into 16p11.2- And 22q11.2-Related Disorders: A Mini-Review.Current genomics · 2025Review
- Effects of an antimicrobial peptide on transport- and novel environment-induced stress in British Shorthair cats.Frontiers in veterinary science · 2025Article
- L-Proline Alters Energy Metabolism in Brain Cortical Tissue Slices.Neurochemical research · 2024Article
- Article
- Atypical cortical networks in children at high-genetic risk of psychiatric and neurodevelopmental disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia.Schizophrenia bulletin · 2023Article
- Mitochondrial proteins encoded by the 22q11.2 neurodevelopmental locus regulate neural stem and progenitor cell proliferation.Molecular psychiatry · 2023Article
- Dopaminergic Modulation of Prefrontal Cortex Inhibition.Biomedicines · 2023Review
- Mitochondrial genes in the 22q11.2 deleted region regulate neural stem and progenitor cell proliferation.bioRxiv : the preprint server for biology · 2023Article
- Proline Metabolism in Neurological and Psychiatric Disorders.Molecules and cells · 2022Review
- [Variations in fecal microbiota of first episode schizophrenia associated with clinical assessment and serum metabolomics].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Proline dehydrogenase (PRODH), which degrades L-proline, resides within the schizophrenia-linked 22q11.2 deletion suggesting a role in disease. Supporting this, elevated L-proline levels have been shown to increase risk for psychotic disorders. Despite the strength of data linking PRODH and L-proline to neuropsychiatric diseases, targets of disease-relevant concentrations of L-proline have not been convincingly described. Here, we show that Prodh-deficient mice with elevated CNS L-proline display specific deficits in high-frequency GABA-ergic transmission and gamma-band oscillations. We find that L-proline is a GABA-mimetic and can act at multiple GABA-ergic targets. However, at disease-relevant concentrations, GABA-mimesis is limited to competitive blockade of glutamate decarboxylase leading to reduced GABA production. Significantly, deficits in GABA-ergic transmission are reversed by enhancing net GABA production with the clinically relevant compound vigabatrin. These findings indicate that accumulation of a neuroactive metabolite can lead to molecular and synaptic dysfunction and help to understand mechanisms underlying neuropsychiatric disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.