Evidence map›Paper›PMID 42754703›Full record

ArticleActa pharmacologica Sinica2026

Small-molecule-induced neuron-specific hypoxia: recapitulating developmental angiogenesis for ischemic stroke therapy.

Xiao-Ying Wang, Zi-Yin Huang, Rui Han, Xin-Yu Li, Yan-Mei Song, Qi Wang, Fu-You Xu, Zi-Hui Zhu, Rong Cheng, Hao-Yu Wu and 6 more

Abstract read
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Article in Acta pharmacologica Sinica, 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

What it found

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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

16 authors.

Xiao-Ying Wang *Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Zi-Yin Huang *Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Rui Han *Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Xin-Yu LiJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Yan-Mei SongJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Qi WangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Fu-You XuDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Zi-Hui ZhuJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
Rong ChengJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Hao-Yu WuJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Yi-Qing XiaJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
Hai-Gang RenJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Xiao-Fan PanDepartment of Neurology, Wuxi Huishan District People's Hospital, Wuxi, 214187, China. pxfwx0510@163.com.
Guo-Dong XiaoDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. gdxiao@suda.edu.cn.
Jian ChengDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. chengjian@suda.edu.cn.
Jia JiaJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. jiajia@suda.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia has therapeutic potential, but global hypoxia is toxic. Inducing safe, cell-specific hypoxia remains a clinically unmet need. We hypothesized that small-molecule-augmented oxygen consumption in adjacent cells induces neuron-specific hypoxia, representing a safe ischemic stroke strategy that mimics neural-directed developmental neovascularization. Using single-cell sequencing, a hypoxic probe, and knockout mice, we showed that ADT-OH (an active metabolite of a hepatoprotective drug) targeted sulfide-quinone oxidoreductase (SQR) to increase aerobic respiration in microglia/macrophages, thereby generating neuron-specific hypoxia after cerebral ischemia. Neuronal hypoxia promoted functional angiogenesis by specifically stabilizing hypoxia-inducible factor to upregulate the expression of neuron-derived vascular endothelial growth factor, supporting a neural-directed angiogenic mechanism. ADT-OH also restored the blood-brain barrier (BBB) via microglial/macrophage SQR. Notably, microglia/macrophage UCP2, the downstream mediator of SQR, was required for ADT-OH-induced BBB repair but not angiogenesis. Mechanistically, ADT-OH targeted UCP2 to increase Wnt/β-catenin signaling, which has been shown to mediate developmental BBB formation. In summary, one small molecule targeting SQR achieves therapeutic cell-specific hypoxia.

Indexed as

angiogenesisblood-brain barrierhypoxiaischemic strokesulfide-quinone oxidoreductase

Identifiers

PMID42754703

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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.