ArticleProceedings of the National Academy of Sciences of the United States of America2017
Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
What it found
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Who cites it
141 citing papers in PubMed, 235 citations in OpenAlex.
- Single-nucleus transcriptomic analysis reveals subfield-specific cell-to-cell synaptic reorganisation of the mouse hippocampus in focal temporal lobe epilepsy.Journal of translational medicine · 2026Article
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- Astrocytic lipid dysregulation as an early driver of neurodegeneration.Nature reviews. Neurology · 2026Review
- Astrocytes in Multiple Sclerosis: Getting to the Core.International journal of molecular sciences · 2026Review
- Astrocytic HMGCR-Mediated Cholesterol Alleviated Parkinson's Disease Phenotypes by Inhibiting NF-κB Neuroinflammation.Molecular neurobiology · 2026Article
- 7-ketocholesterol contributes to microglia-driven increases in astrocyte reactive oxygen species in a mouse model of Alzheimer's disease.Scientific reports · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Lipid metabolism and neurodegeneration: Mechanistic insights and therapeutic targets.Ageing research reviews · 2026Review
- A dual role for cGAS in shaping cellular and organismal responses to genomic instability.Genes & development · 2026Article
- Insulin receptorNature communications · 2026Article
- Radiation-activated astrocytes promote tumor progression through CXCL12 secretion and induce resistance to anti-PD-1 immunotherapy.Translational cancer research · 2026Article
- Neuronal Cholesterol Deficiency Mediated by Astrocytic SREBP2 Downregulation Leads to Postoperative Cognitive Dysfunction Through Impairment of Hippocampal Synaptic Plasticity and Excitatory Synaptic Transmission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular mechanisms of brain lipid metabolism in health and disease.Nature cell biology · 2026Review
- Zebrafish screen of schizophrenia risk genes reveals convergent dysregulation of cholesterol metabolism.bioRxiv : the preprint server for biology · 2026Article
- Radiosynthesis and Evaluation ofACS medicinal chemistry letters · 2026Article
- Astrocytic Cholesterol Fine-Tunes the Balance of Different Modes of Synaptic Exo- and Endocytosis.bioRxiv : the preprint server for biology · 2026Article
- Cell-specific effects of acute sleep deprivation on transcriptomic signatures of non-neuronal cells in the mouse hippocampus and prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- Sleep loss induces cholesterol-associated myelin dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism.Nature genetics · 2026Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances neurite outgrowth, and this is reduced with SREBP2 knockdown astrocytes. In vivo, mice with knockout of SREBP2 in astrocytes have impaired brain development and behavioral and motor defects. These mice also have altered energy balance, altered body composition, and a shift in metabolism toward carbohydrate oxidation driven by increased glucose oxidation by the brain. Thus, SREBP2-mediated cholesterol synthesis in astrocytes plays an important role in brain and neuronal development and function, and altered brain cholesterol synthesis may contribute to the interaction between metabolic diseases, such as diabetes and altered brain function.
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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.