Evidence mapPaperPMID 42593697Full record

ArticleMolecular neurobiology2026

TMC6 Protects Against Ischemic Neuronal Injury by Activating Rap1/Rac1 Signaling to Restore Mitochondrial Dynamics and Mitophagy.

Xuemei Quan, Huo Liang, Haiyin Long, Xiawei Wang, Liling Feng, Xia Zhou, Yuan Chen, Yanhua Li, Xiaofeng Li

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Article in Molecular neurobiology, 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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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Xuemei QuanDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Institute of Brain and Mental Diseases, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China.
Huo LiangDepartment of Rehabilitation, Guangxi International Zhuang Medicine Hospital, Nanning, Guangxi, 530000, China.
Haiyin LongDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China.
Xiawei WangDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China.
Liling FengDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China.
Xia ZhouDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China.
Yuan ChenDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China. yuanchengxyy@163.com.
Yanhua LiDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Institute of Brain and Mental Diseases, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China. 13978604622@163.com.
Xiaofeng LiDepartment of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Institute of Brain and Mental Diseases, Guangxi Academy of Medical Sciences, No. 6 Taoyuan Road, Nanning, Guangxi, 530021, China. xiaofengLi_sjnk@163.com.

Funding

Guangxi Natural Science Foundation of China 2023GXNSFBA026159Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects Z-A20220024National Natural Science Foundation of China 82160239
6 · The paper itself

Abstract

Ischemic stroke (IS) is a leading cause of neurological disability, yet the molecular basis of neuronal injury and repair remains unclear. Three Gene Expression Omnibus datasets (GSE22255, GSE58294, and GSE37587) were integrated for differential expression analysis. Candidate genes were identified by combining protein-protein interaction network analysis with weighted gene co-expression network analysis and validated in GSE16561. The effects of transmembrane channel-like 6 (TMC6) were investigated in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated HT22 cells and a rat middle cerebral artery occlusion (MCAO) model. Rap1/Rac1-related signaling was examined using geranylgeranyltransferase I inhibitor-298 (GGTI-298) and Rac1 knockdown. TMC6 was downregulated in IS. TMC6 overexpression reduced cortical and striatal infarction and mitigated neurological deficits in the MCAO rat. TMC6 overexpression alleviated neuronal apoptosis and improved cell viability in OGD/R-treated HT22 cells. Inflammatory response was suppressed, and mitochondrial membrane potential was preserved after TMC6 overexpression. TMC6 reprogrammed mitochondrial dynamics and quality control by increasing mitofusin 1 (MFN1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), suppressing dynamin-related protein 1 (DRP1), and restoring the expression of the mitophagy-associated proteins PTEN-induced putative kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (Parkin). TMC6 knockdown exacerbated OGD/R-induced injury.. Pharmacological inhibition of Rap1 using GGTI-298 or genetic silencing of Rac1 markedly abrogated TMC6-mediated neuroprotection. TMC6 alleviates experimental ischemic neuronal injury and preserves mitochondrial homeostasis. Rap1/Rac1-related signaling may be involved in these protective effects. These findings identify TMC6 as a potential therapeutic target for IS.

Indexed as

Brain IschemiaMitochondrial DynamicsMitophagyNeuronsrac1 GTP-Binding Proteinrap1 GTP-Binding ProteinsSignal TransductionAnimalsApoptosisCell LineGlucoseInfarction, Middle Cerebral ArteryIschemic StrokeMaleMiceMitochondriaGlucoserac1 GTP-Binding Proteinrap1 GTP-Binding ProteinsIschemic strokeMitochondrial dysfunctionRap1/Rac1 signalingTransmembrane channel-like 6

Identifiers

PMID42593697

What Socratic holds

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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 Socratic graph.