ArticleJCI insight2021
Acyl-CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 39 citations in OpenAlex.
- Statin therapy upregulates arachidonic acid status via enhanced endogenous synthesis in patients with plaque psoriasis.Prostaglandins, leukotrienes, and essential fatty acids · 2022Trial
- Functional Annotation of Alzheimer's Disease-Associated SNPs Based on Three-Dimensional Chromatin Structure.International journal of molecular sciences · 2026Article
- Metabolic Adaptation in Acute Ischemic Events: The Critical Role of Acyl-Coenzyme A Synthetase Family in Myocardial Infarction and Ischemic Stroke.Journal of the American Heart Association · 2026Review
- Article
- Roles of ACSL6 in lipid homeostasis and stress responses in the nervous system.Metabolic brain disease · 2026Review
- Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Acsl4-mediated Lipid Homeostasis Orchestrates Synaptic and Cognitive Plasticity.Research square · 2026Article
- Article
- Mitochondria-targeting ACSL6 variant drives mitochondrial fragmentation potentially through local DHA-CoA production.Scientific reports · 2026Article
- Sex- and brain region-specific gene expression in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury.Bone research · 2026Review
- DHA-dominant Omega-3 compositions enhance PSD-95 organization and glutamatergic protein expression.Frontiers in synaptic neuroscience · 2026Article
- Y-shaped trivalent aptamer for targeted visualization and tracking of reprogrammed astrocytes.Materials today. Bio · 2025Article
- ACSL6 modulates docosahexaenoic acid-induced cytotoxicity to potentiate chemotherapy response in colorectal and breast cancer.Oncogenesis · 2025Article
- Inhibition of ACSL6 ameliorates atherosclerosis by suppressing macrophage ferroptosis via the Nrf2 pathway.Molecular biology reports · 2025Article
- Dysregulation of cellular metabolism within the gut-brain axis is associated with behavioural changes in chronic intestinal inflammation.Journal of neuroinflammation · 2025Article
- Aging Effects on Lipid Metabolism in Response to Traumatic Brain Injury.Journal of neurochemistry · 2025Article
- Lysine myristoylation mediates long-term potentiation via membrane enrichment of synaptic plasticity effectors.The EMBO journal · 2025Article
- Circular RNA circBNC2 inhibits tumorigenesis by modulating ferroptosis and acts as a nanotherapeutic target in prostate cancer.Molecular cancer · 2025Article
- Increased ACSL6 Expression Predicts a Favorable Prognosis in Triple-negative Breast Cancer.Current medicinal chemistry · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The omega-3 fatty acid docosahexaenoic acid (DHA) inversely relates to neurological impairments with aging; however, limited nondietary models manipulating brain DHA have hindered a direct linkage. We discovered that loss of long-chain acyl-CoA synthetase 6 in mice (Acsl6-/-) depletes brain membrane phospholipid DHA levels, independent of diet. Here, Acsl6-/- brains contained lower DHA compared with controls across the life span. The loss of DHA- and increased arachidonate-enriched phospholipids were visualized by MALDI imaging predominantly in neuron-rich regions where single-molecule RNA in situ hybridization localized Acsl6 to neurons. ACSL6 is also astrocytic; however, we found that astrocyte-specific ACSL6 depletion did not alter membrane DHA because astrocytes express a non-DHA-preferring ACSL6 variant. Across the life span, Acsl6-/- mice exhibited hyperlocomotion, impairments in working spatial memory, and increased cholesterol biosynthesis genes. Aging caused Acsl6-/- brains to decrease the expression of membrane, bioenergetic, ribosomal, and synaptic genes and increase the expression of immune response genes. With age, the Acsl6-/- cerebellum became inflamed and gliotic. Together, our findings suggest that ACSL6 promotes membrane DHA enrichment in neurons, but not in astrocytes, and is important for neuronal DHA levels across the life span. The loss of ACSL6 impacts motor function, memory, and age-related neuroinflammation, reflecting the importance of neuronal ACSL6-mediated lipid metabolism across the life span.
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.