Evidence map›Paper›PMID 42310739›Full record

ArticleJournal of biomedical science2026

ENT1 inhibitor J4 restores cognitive function and white-matter integrity in a mouse model of tuberous sclerosis complex.

Christine Chin-Jung Hsieh, Yi-Syue Tsou, Nai-Kuei Huang, Ting-Chieh Chen, Ssu-Ju Li, Ching-Wen Chang, Wei-Xuan Lin, Szu-Yu Tung, Yijuang Chern, You-Yin Chen and 1 more

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Article in Journal of biomedical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Christine Chin-Jung HsiehTaipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
Yi-Syue Tsou *Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
Nai-Kuei Huang *National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
Ting-Chieh ChenDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei, 11221, Taiwan.
Ssu-Ju LiDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei, 11221, Taiwan.
Ching-Wen ChangDepartment of Biomedical Engineering, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong St., Taipei, 11221, Taiwan.
Wei-Xuan LinPh.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, No. 250, Wu-Hsin St., Taipei, 11031, Taiwan.
Szu-Yu TungBiomedical Translation Research Center, Academia Sinica, Taipei, Taiwan.
Yijuang ChernBiomedical Translation Research Center, Academia Sinica, Taipei, Taiwan.
You-Yin ChenPh.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, No. 250, Wu-Hsin St., Taipei, 11031, Taiwan. irradiance@so-net.net.tw.
Yi-Chao LeePh.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, No. 250, Wu-Hsin St., Taipei, 11031, Taiwan. yclee@tmu.edu.tw.ORCID https://orcid.org/0000-0003-3451-183X

Funding

Academia Sinica, Taiwan AS-KPQ-111-KNTHigher Education Sprout Project DP2-TMU-113-N-01National Science and Technology Council of Taiwan NSTC110-2320-B-038-016-MY3Taipei Medical University Hospital TMU-114-N-01
6 · The paper itself

Abstract

backgroundTuberous sclerosis complex (TSC) is a hereditary disease caused by pathogenic mutations in the TSC1 or TSC2 genes, leading to overactivation of mTOR signaling and dysregulation of downstream pathways. The majority of individuals with TSC develop psychiatric and neurodevelopmental comorbidities-including intellectual disability, autism spectrum disorders, anxiety and other behavioral manifestations-collectively termed TSC-associated neuropsychiatric disorders. Over the past decade, increasing evidence from clinical and preclinical studies has highlighted a significant myelination deficit in the brains of TSC patients and animal models. Although mTOR inhibition can alleviate myelination defects and improve cognition in rodent models, clinical studies using the mTOR inhibitor, everolimus, has limited cognitive benefits in TSC individuals. Adenosine signaling has been recognized as a key player in oligodendrocyte maturation and myelin formation and may represent a promising target for therapeutic intervention.

methodsIn the present study, we treated Tsc2

resultsJ4 treatment improved both cognitive deficits and anxiety-like behavior in Tsc2

conclusionAltogether, these findings indicate that J4 modulates oligodendroglial lineage populations, enhances myelination, and improves neural connectivity by regulating neuronal hyperactivity. Our results suggest that J4 is a strong therapeutic candidate for addressing the neuropsychiatric manifestations of TSC.

Indexed as

CognitionTuberous SclerosisWhite MatterAnimalsDisease Models, AnimalMaleMiceTuberous Sclerosis Complex 2 ProteinTsc2 protein, mouseTuberous Sclerosis Complex 2 ProteinAdenosineCNS myelinationEquilibrative nucleoside transporter 1Oligodendroglial maturationTuberous sclerosis complexWhite matter

Identifiers

PMID42310739
PMCPMC13274077

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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.