ArticleEMBO molecular medicine2016
Molecular cause and functional impact of altered synaptic lipid signaling due to a prg-1 gene SNP.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Genetic Determinants of Gating Functions: Do We Get Closer to Understanding Schizophrenia Etiopathogenesis?Frontiers in psychiatry · 2020Pooled it
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Targeted lipidomics dataset of central nervous system and plasma from mice with experimental autoimmune encephalomyelitis.Data in brief · 2025Article
- PRG-1 Relieves Neonatal Stimuli-Induced Hyperalgesia and Anxiety via Stage-Specific Synapse Remodeling.CNS neuroscience & therapeutics · 2025Article
- Article
- Altered cortical synaptic lipid signaling leads to intermediate phenotypes of mental disorders.Molecular psychiatry · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Lysophosphatidic Acid Receptors LPAR5 and LPAR2 Inversely Control Hydroxychloroquine-Evoked Itch and Scratching in Mice.International journal of molecular sciences · 2024Article
- Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress.Neurobiology of stress · 2024Article
- Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions.Frontiers in immunology · 2024Article
- LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Investigation into Molecular Brain Aging in Senescence-Accelerated Mouse (SAM) Model Employing Whole Transcriptomic Analysis in Search of Potential Molecular Targets for Therapeutic Interventions.International journal of molecular sciences · 2023Article
- Autism Spectrum Disorder: A Neuro-Immunometabolic Hypothesis of the Developmental Origins.Biology · 2023Article
- Preserving stroke penumbra by targeting lipid signalling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Modulation of working memory duration by synaptic and astrocytic mechanisms.PLoS computational biology · 2022Article
- PRG-1 prevents neonatal stimuli-induced persistent hyperalgesia and memory dysfunction via NSF/Glu/GluR2 signaling.iScience · 2022Article
- Plasma membrane phospholipid phosphatase-related proteins as pleiotropic regulators of neuron growth and excitability.Frontiers in molecular neuroscience · 2022Review
- Lysophosphatidic Acid Signalling in Nervous System Development and Function.Neuromolecular medicine · 2021Review
- Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2.Cellular and molecular life sciences : CMLS · 2021Article
- PRG-1 relieves pain and depressive-like behaviors in rats of bone cancer pain by regulation of dendritic spine in hippocampus.International journal of biological sciences · 2021Article
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31 authors at 6 institutions in 2 countries.
Funding
Abstract
Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases.
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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.