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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan Zhou Hongdong Zhao Ye Hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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