Evidence map›Paper›PMID 40471331›Full record

ArticleCellular and molecular life sciences : CMLS2025

The ADCY1-mediated cAMP signaling pathway mediates functional effects of montelukast treatment in brain organoids.

Zhenhong Xu, Hongye Yan, Bo Wang, Huimin Wang, Ye Xia, Juan Wan, Jiamei Jiang, Lin Zeng, Beisha Tang, Qingtuan Meng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Zhenhong Xu *The First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Hongye Yan *The First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Bo Wang *The First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Huimin WangThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Ye XiaThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Juan WanThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Jiamei JiangThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. 645649828@qq.com.
Lin ZengThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. 2854686580@qq.com.
Beisha TangThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. bstang7398@163.com.
Qingtuan MengThe First Affiliated Hospital, Multi-Omics Research Center for Brain Disorders, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. mengqingtuan@glmc.edu.cn.ORCID http://orcid.org/0000-0002-6421-162X

Funding

National Natural Science Foundation of China 81901359National Natural Science Foundation of China 82171504Natural Science Foundation of Hunan Province 2022JJ20035Science and Technology Innovation Program of Hunan Province 2022RC1214
6 · The paper itself

Abstract

Montelukast (MTK) is a drug widely used for treating allergic rhinitis and asthma. However, severe neuropsychiatric adverse events related to MTK have been reported, with limited understanding of the underlying mechanisms. Here we leveraged human forebrain organoids (hFOs) and showed that MTK exposure in hFOs downregulated the expression of genes associated with multiple neuronal functions and neuropsychiatric disorders. The following integrative analysis highlighted adenylate cyclase 1 (ADCY1), a main regulator of the cAMP signaling pathway, as a hub gene mediating the functional effects of MTK exposure. We also showed that MTK exposure resulted in a reduction of cAMP and neuroactivities, and caused neural maturation defects. These cellular phenotypes could be recapitulated by treating hFOs with ST034307, a selective ADCY1 inhibitor, or partially rescued by ADCY1 overexpression in hFOs. Together, this study underscored that MTK exposure caused neuropsychiatric effects through inhibiting the ADCY1-mediated cAMP signaling pathway.

Indexed as

AcetatesAdenylyl CyclasesBrainCyclic AMPCyclopropanesOrganoidsQuinolinesSignal TransductionSulfidesHumansProsencephalonAcetatesadenylyl cyclase 1Adenylyl CyclasesCyclic AMPCyclopropanesmontelukastQuinolinesSulfidesADCY1CAMP signaling pathwayGPCRsHuman forebrain organoidsMontelukastNeuropsychiatric effects

Identifiers

PMID40471331
PMCPMC12141180

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.