Systematic Identification of Therapeutic Targets and Repurposed Drugs for Stroke: From Genome Causal Analysis to Multilevel Validation.
Overview
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
- Department of Neurology, Aerospace Medical Center, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China
- Department of Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing, China
Abstract
Background: Stroke is a severe cerebrovascular disease characterized by narrow time windows and complications. This study aimed to identify novel drug targets and repurposed drugs for stroke.
Methods: This study used expression quantitative trait loci data from druggable genes in brain and blood as instrumental variables. Mendelian randomization, colocalization, and phenome‐wide Mendelian randomization were applied to evaluate causal relationships and potential side effects, with stroke and ischemic stroke as primary outcomes. Preclinical validation used oxygen–glucose deprivation/
Results: Elevated GGCX expression in brain and blood was potentially causally associated with reduced risk of stroke and ischemic stroke, supported by colocalization evidence, although potential cardiovascular risks could not be excluded. Drug repositioning identified ifenprodil as a candidate agent that reduced infarction volume, improved motor and cognitive functions, and reversed GGCX downregulation in mice. Ifenprodil treatment and GGCX overexpression alleviated oxygen–glucose deprivation/
Conclusions: This study established a potential causal link between GGCX and stroke risk, particularly ischemic stroke. GGCX represents a promising therapeutic target for ischemic stroke. Targeted GGCX expression upregulation and drug repurposing, particularly ifenprodil, may offer novel therapeutic avenues. Further validation is warranted to assess clinical efficacy and safety.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Code
No file of the authors' code could be read here: it is described below, and read at its source.
AzumitoAsneuet112358/MR-Target-in-STROKE
Availability: 1 check, the latest on 27 September 2026: the link is dead
- 27 September 2026: the link is dead
The paper's code and data availability statement is in the Data section.
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Data
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Data Sources, Code Availability, and Approval
The original contributions presented in the study are included in the article or the Supplemental Material. Further inquiries can be directed to the corresponding authors. The study codes can be accessed at GitHub (https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 8 keywords, 17 MeSH terms, 70 references.
Cite
This paper
Zhang, X., Zhang, Y., Li, J., Wang, W., Tu, W., & Wang, H. (2026). Systematic Identification of Therapeutic Targets and Repurposed Drugs for Stroke: From Genome Causal Analysis to Multilevel Validation. Journal of the American Heart Association, 15(13), e046088. https://
BibTeX
@article{zhang2026system
author = {Zhang, Xia and Zhang, Yi‐Ming and Li, Ji‐Lai and Wang, Wei and Tu, Wen‐Jun and Wang, Hong‐Qi},
title = {{Systematic Identification of Therapeutic Targets and Repurposed Drugs for Stroke: From Genome Causal Analysis to Multilevel Validation}},
journal = {Journal of the American Heart Association},
year = {2026},
month = jun,
volume = {15},
number = {13},
pages = {e046088},
publisher = {Wiley},
issn = {2047-9980},
doi = {10.1161/
url = {https://
pmid = {42333666},
pmcid = {PMC13477297}
}
RIS
TY - JOUR
AU - Zhang, Xia
AU - Zhang, Yi‐Ming
AU - Li, Ji‐Lai
AU - Wang, Wei
AU - Tu, Wen‐Jun
AU - Wang, Hong‐Qi
TI - Systematic Identification of Therapeutic Targets and Repurposed Drugs for Stroke: From Genome Causal Analysis to Multilevel Validation
T2 - Journal of the American Heart Association
J2 - J Am Heart Assoc
PY - 2026
DA - 2026/
VL - 15
IS - 13
SP - e046088
SN - 2047-9980
PB - Wiley
DO - 10.1161/
UR - https://
LA - en
ER -
CSL-JSON
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