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Anti-asthma drug Montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling [RNA-seq and Ribo-seq]

GSE232669 Homo sapiens Expression profiling by high throughput sequencing; Other 18 samples Submitted 2026/03/16 Platform GPL16791
Summary
Globally, autism spectrum disorder (ASD) affects approximately 1.0-2.5% of human newborns, with non-genetic risk factors estimated to contribute to over 50% ASD cases through yet elusive mechanisms. Montelukast (MTK), a leukotriene receptor antagonist and FDA-approved anti-asthma drug, was found to potently disrupt retinoic acid (RA) signaling, and substantially increase the risk of ASD in humans when used during pregnancy or in early childhood, according to prospective and retrospective cohort studies. Both maternal and postnatal exposure to montelukast caused autistic-like behaviors in rat offspring. Montelukast also altered brain regional patterning through disrupting RA signaling in human cerebral organoids, similar to DEAB, an established inhibitor of RA-synthesizing ALDH1As. Mechanistically, montelukast was found to directly bind to retinoic acid receptor alpha (RARα) and impair RARα heterodimer formation to disrupt RA signaling. Altogether, this work highlighted not only the developmental origin of ASD, but the utmost importance in cautioned use of medicinal chemicals during maternity or early childhood to prevent psychiatric disorders, e.g. ASD.
Published in
Anti-asthma drug montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling
Hao ZJ, Wu QH, Li YL et al. · Signal transduction and targeted therapy 2026 · PMID 42230569 · doi:10.1038/s41392-026-02665-w
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Direct links to NCBI, no account and no request form: the whole study as GSE232669_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 18 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA973551 and SRA study SRP438172. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
Brain Organoid, DMSO, Day 60, RNAseq, biol ×3 Brain Organoid, DEAB, Day 60, RNAseq, biol ×3 Brain Organoid, MTK, Day 60, RNAseq, biol ×3 Brain Organoid, DMSO, Day 60, Riboseq, biol ×3 Brain Organoid, DEAB, Day 60, Riboseq, biol ×3 Brain Organoid, MTK, Day 60, Riboseq, biol ×3

Supports a between-group comparison across 18 samples.

6 replicated groups read from 18 sample titles; they account for 18 of them. Check it against the sample list below before relying on it.

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