ArticleProceedings of the National Academy of Sciences of the United States of America2022
Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
- A Unified Framework for Spinal Cord Injury Repair: Metabolic-Nutritional Microenvironment Remodeling, Immune Modulation, and Neural Regeneration.Molecular neurobiology · 2026Review
- Dysregulated adult hippocampal neurogenesis in major depressive disorder.Nature medicine · 2026Article
- Dual antitumor and neuroprotective activities of lipid ether amide hybrids in glioma cells and metabolically damaged neurons.Biochemistry and biophysics reports · 2026Article
- An Activator of Tailless' Repressor Function Stimulates Anti-Neurodegenerative Gene Expression.Journal of medicinal chemistry · 2026Article
- Regulatory networks involved in modulating fat deposition in pigs identified by gene co-expression analysis.BMC genomics · 2026Article
- Integration of Metabolic Pathways and Micronutrient Signals Influences Neurodevelopment by Modulating Neural Stem Cell Dynamics.Molecular neurobiology · 2026Review
- Review
- Oleic acid improves pathological changes in Aβ1-42-induced astrocytes and Alzheimer's disease mouse models through PKA/ACACB/CPT1A.Frontiers in neuroscience · 2026Article
- Review
- A Longitudinal Study of Baseline Fatty Acid Concentrations and Executive Function Over 12 Months Among Adolescents With and Without Perinatal HIV Exposure or Infection From Kampala, Uganda.The Journal of nutrition · 2025Article
- The multifaceted roles of fatty acids and their dysregulation in obese mothers: potential implications for infant development.Nutrition & metabolism · 2025Review
- Peri- and Postnatal High Fat Feeding Have Differential Effects on Executive Function and Associated Neurobiology in Aged Male and Female Mice.Aging cell · 2025Article
- The Construction of a Mutant Library of Linseed and the Molecular Mechanism of High Oleic Acid Mutants from a Multi-Omics Perspective.Plants (Basel, Switzerland) · 2025Article
- Stearoyl-CoA desaturase-1: a potential therapeutic target for neurological disorders.Molecular neurodegeneration · 2024Review
- Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors.British journal of cancer · 2024Article
- Hyperbaric Oxygen Improves Cognitive Impairment Induced by Hypoxia via Upregulating the Expression of Oleic Acid and MBOAT2 of Mice.Antioxidants (Basel, Switzerland) · 2024Article
- MicroRNAs: pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy.Translational psychiatry · 2024Review
- Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation.Molecular neurobiology · 2024Review
- Review
- Effects of saturated and monounsaturated fatty acids on cognitive impairment: evidence from Mendelian randomization study.European journal of clinical nutrition · 2024Article
Corrections and comments
- Commented on by
Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
Abstract
Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.