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journal article·2026-02Open access

AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition and Lipid Droplets Accumulation

Junqiu Jia, Yonghui Gan, Jia Li, Lilin Li, Hailan Meng, Min Sun, Lei Ye, Rui Mao, Xiang Cao, Shengnan Xia, Xinyu Bao, Renyuan Liu, Meijuan Zhang, Yun Xu

Advanced Science· Volume 13· Issue 10
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Abstract

ABSTRACT Ischemic white matter injury leads to long‐term neurological deficits but currently lacks effective therapies. Although AXL has been implicated in debris clearance and inflammatory regulation, its role in post‐stroke myelin repair remains unclear. Here, we report robust upregulation of microglial AXL in mice after tMCAO. Microglial AXL cKO mice exhibited worse motor and cognitive deficits up to 28 days after tMCAO, accompanied by more severe white matter damage, increased myelin debris, and greater lipid droplets (LDs) accumulation in microglia than WT controls. Longitudinal analysis showed that AXL‐deficient microglia had reduced early phagocytic capacity but increased LDs accumulation and lipid peroxidation at later stages. Transcriptomic profiling revealed altered inflammatory and sphingolipid metabolism pathways in AXL‐deficient microglia. Mechanistically, AXL regulates Smpd1 transcription via EGR1, thereby modulating sphingolipid metabolism and LDs accumulation. Remarkably, supplement with ASM (the Smpd1 ‐encoded enzyme) in AXL cKO mice reduced LDs accumulation and attenuated ischemic white matter injury. Collectively, these findings identify microglial AXL as an endogenous regulator of myelin repair after ischemic stroke.
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Research context

Materials processing

OpenAlex topics: Phagocytosis and Immune Regulation · Neuroinflammation and Neurodegeneration Mechanisms · Autophagy in Disease and Therapy

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Neurology Nanjing Drum Tower Hospital Chinese Academy of Medical Science & Peking Union Medical College Nanjing China

Department of Emergency Medicine Nanjing Drum Tower Hospital Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing China

Department of Neurology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing China

State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing University Nanjing China

Jiangsu Key Laboratory for Molecular Medicine and Institute of Translational Medicine for Brain Critical Diseases Nanjing University Nanjing China

Jiangsu Provincial Key Discipline of Neurology Nanjing China

Nanjing Neurology Clinical Medical Center and Nanjing Gulou Hospital Brain disease and brain Science Center Nanjing China

Department of Radiology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Jiangsu Province

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