Degradation of LOX-1 via Neuronal Autophagy Alleviates Cerebral Ischemia/Reperfusion Injury in Mice.

Yue Hu, Yangmin Zheng, Tong Shen, Rongliang Wang, Feng Yan, Zhen Tao, Yumin Luo, Ping Liu

Abstract read

In one paragraph

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.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yue Hu *Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Yangmin Zheng *Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Tong ShenInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Rongliang WangInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Feng YanInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Zhen TaoInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Yumin LuoInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China. yumin111@ccmu.edu.cn.

Ping LiuInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China. pingliu@xwhosp.org.

Funding

Natural Science Foundation in China 82001390Natural Science Foundation in China 82371306

6 · The paper itself

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is critically involved in atherosclerotic plaque formation. Recent clinical evidence suggest that the LOX-1 polymorphisms are linked to the susceptibility and outcomes of ischemic stroke (IS). However, the mechanisms through which LOX-1 influences cerebral ischemia/reperfusion (I/R) injury are not fully understood. In this study, blood samples were obtained from 295 patients with acute IS (AIS), and parallel experimental models including middle cerebral artery occlusion and reperfusion (MCAO/R) in male C57BL/6 mice and oxygen glucose deprivation (OGD) in primary neurons, were used to simulate cerebral I/R injury. Elevated serum soluble LOX-1 (sLOX-1) levels were detected in patients with AIS and showed positive correlations with both infarct volume and the 3-month modified Rankin scale (mRS) score. In mice, LOX-1 overexpression increased infarct volume, aggravated neurological deficits, and reduced cerebral blood flow (CBF), whereas LOX-1 knockdown produced the opposite effects. Co-immunoprecipitation demonstrated that LOX-1 interacts with key autophagy-lysosome pathway proteins (LC3B, P62, and LAMP2) in primary neurons. Western blotting, immunofluorescence and transmission electron microscopy showed that LOX-1 overexpression suppresses neuronal autophagic flux in peri-infarct brain tissue, while LOX-1 knockdown restores it. Moreover, early activation of autophagy with rapamycin (RAPA) promoted LOX-1 degradation, reduced infarct volume, improved neurological deficits, and restored CBF following cerebral I/R. Collectively, these findings indicated that LOX-1 exacerbates cerebral I/R injury by inhibiting neuronal autophagic flux. Early autophagy activation may therefore represent a promising neuroprotective strategy by facilitating LOX-1 degradation during acute cerebral ischemia.

Indexed as

AutophagyBrain IschemiaNeuronsProteolysisReperfusion InjuryScavenger Receptors, Class EAnimalsHumansInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLOlr1 protein, mouseScavenger Receptors, Class EAutophagic fluxIschemia reperfusion/injuryLectin-like oxidized low-density lipoprotein receptor-1Neuronal autophagyNeuroprotection

Identifiers

PMID41699375

DOI10.1007/s12035-026-05730-1

PMCPMC12909471

What Socratic holds

Textmetadata

LicenceCC BY-NC-ND

Read underepoch 390

Registered trials

None linked

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.