Inhibition of SLC11A1‐Mediated Lysosomal Iron Accumulation in Microglia Promotes Repair Following White Matter Stroke
Source abstract
Abstract
ABSTRACT White matter stroke (WMS) results in demyelinating changes and neurological deficits. However, the underlying molecular mechanisms of demyelination after stroke and the specific role of microglia in white matter rehabilitation remain incompletely elucidated. This study identifies a time‐dependent accumulation of iron in microglial lysosomes mediated by solute carrier family 11 member 1 (SLC11A1), which persists from 12 h to 14 days following WMS. This iron accumulation results in damaged lysosomal myelin debris uptake and degradation in microglia. Notably, iron chelation with deferoxamine (DFO), microglia‐specific knockdown of SLC11A1, and administration of LM22B‐10, a SLC11A1 antagonist identified in this study, effectively reduce lysosomal iron accumulation in microglia, enhance microglial uptake and clearance of myelin debris, and ultimately promote functional recovery after WMS. Furthermore, SLC11A1 functions as a H + /Fe 2+ antiporter that transports Fe 2+ from the cytoplasm into lysosomes both in vitro and in vivo. Collectively, these results highlight that targeting SLC11A1 represents a previously unrecognized therapeutic strategy for WMS repair with significant clinical implications.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Lysosomal Storage Disorders Research · Neuroinflammation and Neurodegeneration Mechanisms · Parkinson's Disease Mechanisms and Treatments
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow University Suzhou China
Department of Neurology Taizhou Municipal Hospital (Taizhou University Affiliated Municipal Hospital) School of Medicine Taizhou University Taizhou China
Department of Neurology Huai'an Fifth People's Hospital Huai'an Hospital Affiliated to Yangzhou University Huai'an China
Jiangsu Key Laboratory of Drug Discovery and Translational Research For Brain Diseases Institute of Neuroscience Soochow University Suzhou China
Jiangsu Key Laboratory of Drug Discovery and Translational Research For Brain Diseases College of Pharmaceutical Sciences Soochow University Suzhou China
Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases Soochow University Suzhou China
Funding
National Natural Science Foundation of China · Second Affiliated Hospital of Soochow University · Taizhou Municipal Science and Technology Bureau
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