ArticleScience advances2023
Leukotriene A4 hydrolase inhibition improves age-related cognitive decline via modulation of synaptic function.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- Yucca filamentosa extract therapeutic potential against neuro-inflammation and demyelination through modulation of eicosanoids.Inflammopharmacology · 2026Article
- Reconstruction of human metabolic models with large language models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Comparative transcriptomic analysis of embryonic stem cells across mammalian species.iScience · 2026Article
- The Nodding syndrome cerebrospinal fluid proteome: a lens into neurodevelopmental failure consistent with environmentally triggeredFrontiers in molecular neuroscience · 2026Article
- Arachidonic acid protects against diabetes-induced atrial fibrillation.Lipids in health and disease · 2025Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukotrienes, a class of inflammatory bioactive lipids, are well studied in the periphery, but less is known of their importance in the brain. We identified that the enzyme leukotriene A4 hydrolase (LTA4H) is expressed in healthy mouse neurons, and inhibition of LTA4H in aged mice improves hippocampal dependent memory. Single-cell nuclear RNA sequencing of hippocampal neurons after inhibition reveals major changes to genes important for synaptic organization, structure, and activity. We propose that LTA4H inhibition may act to improve cognition by directly inhibiting the enzymatic activity in neurons, leading to improved synaptic function. In addition, LTA4H plasma levels are increased in both aging and Alzheimer's disease and correlated with cognitive impairment. These results identify a role for LTA4H in the brain, and we propose that LTA4H inhibition may be a promising therapeutic strategy to treat cognitive decline in aging related diseases.
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Registered trials
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