Evidence map›Paper›PMID 41483356›Full record

ArticleJournal of molecular neuroscience : MN2026

LDHA as a Potential Therapeutic Target for Lactylation Regulation in Spinal Cord Injury: Integrated Bioinformatics Analysis, Experimental Validation, and Drug Prediction.

Bobo Zhang, Shenglong Wang, Wenting Xu, Xiaochen Su, Yulong Zhang, Ziliang Lu, Zhan Zhang, Yingang Zhang

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Article in Journal of molecular neuroscience : MN, 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.

2 · The registry

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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

8 authors.

Bobo ZhangDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China.
Shenglong WangDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China.
Wenting XuThe Second Affiliated Hospital of Xian Jiaotong University, Xian, China.
Xiaochen SuDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China.
Yulong ZhangDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China.
Ziliang LuDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China.
Zhan ZhangDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China.
Yingang ZhangDepartment of Orthopedics, The First Affiliated Hospital of Xian Jiaotong University, Xian, China. zyingang@mail.xjtu.edu.cn.

Funding

the Fundamental Research Funds for the Central Universities No. xzy022025073
6 · The paper itself

Abstract

Lactate metabolism and its epigenetic modification, lactylation, are emerging regulators in neurological disorders, yet their roles in spinal cord injury (SCI) remain unclear. Here, we mined SCI transcriptomes from GEO and identified 13 differentially expressed lactylation-related genes (DE-LRGs), with lactate dehydrogenase A (LDHA) significantly upregulated. Immune-infiltration analysis linked LDHA to T cells gamma delta, and Mfuzz time-series clustering showed dynamic LDHA upregulation during acute SCI, which was validated in GSE45006. Random forest and ROC analyses supported the diagnostic value of LDHA. PPI and GeneMANIA networks positioned LDHA at the intersection of lactate metabolism and immune regulation. Drug prediction with Enrichr/DSigDB and docking highlighted folic acid and quercetin dihydrate as candidate compounds. GSVA/GSEA indicated LDHA enrichment in immune activation, metabolic regulation, and stress-response pathways. Immunofluorescence in a rat SCI model confirmed sustained LDHA elevation from 1 to 3 days around the lesion. Importantly, Western blot validation (3 days post-injury) demonstrated increased nuclear HIF-1α and p-STAT3^Y705 (total STAT3 unchanged) together with elevated CXCL1, IL-6, and CCL2 and the infiltration marker MPO/CD68; these changes were attenuated by LDHA inhibition (FX11) and partially rescued by exogenous lactate, supporting an LDHA → lactate → HIF-1α/STAT3 → chemokine/infiltration axis in acute SCI. Collectively, our data identify LDHA as a key lactylation-related regulator in SCI that contributes to pathogenesis via metabolic reprogramming and immune modulation, highlighting its promise as a diagnostic biomarker and therapeutic target.

Indexed as

Lactic AcidL-Lactate DehydrogenaseSpinal Cord InjuriesAnimalsFolic AcidHypoxia-Inducible Factor 1, alpha SubunitLactate Dehydrogenase 5MaleQuercetinRatsRats, Sprague-DawleySTAT3 Transcription FactorFolic AcidHypoxia-Inducible Factor 1, alpha SubunitLactate Dehydrogenase 5Lactic AcidL-Lactate DehydrogenaseQuercetinSTAT3 Transcription FactorLactate Dehydrogenase ALactylationSpinal Cord Injury

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Registered trials

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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.