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Targeting SARM1 as a novel neuroprotective therapy in neurotropic viral infections

文献类型： 外文期刊

作者： He, Sheng 1 ; Zhu, Yanyan 1 ; Wang, Xinyue 1 ; Zhang, Gaofeng 1 ; Hou, Kaijian 8 ; Xia, Xianzhu 1 ; Jiang, Zhenyou 10 ; Gong, Xiaoqian 7 ; Zhao, Pingsen 1 ;

作者机构： 1.Shantou Univ, Yuebei Peoples Hosp, Med Coll, Dept Lab Med, Shaoguan 512025, Peoples R China

2.Shantou Univ, Yuebei Peoples Hosp, Med Coll, Lab Diag Clin Microbiol & Infect, Shaoguan 512025, Peoples R China

3.Res Ctr Interdisciplinary & High Qual Innovat Dev, Shaoguan 512025, Peoples R China

4.Shantou Univ Med Coll, Yuebei Peoples Hosp, Shaoguan Municipal Qual Control Ctr Lab Med, Shaoguan 512025, Peoples R China

5.Shaoguan Municipal Qual Control Ctr Surveillance B, Shaoguan 512025, Peoples R China

6.Shaoguan Engn Res Ctr Res & Dev Mol & Cellular Tec, Shaoguan 512025, Peoples R China

7.Shantou Univ, Yuebei Peoples Hosp, Med Coll, 133 Huimin Rd South, Shaoguan 512025, Peoples R China

8.Shantou Univ, Sch Publ Hlth, Shantou 515041, Peoples R China

9.Chinese Acad Agr Sci, Changchun Vet Res Inst, Key Lab Jilin Prov Zoonosis Prevent & Control, Changchun, Peoples R China

10.Jinan Univ, Key Lab Viral Pathogenesis & Infect Prevent & Cont, Minist Educ, Guangzhou 510632, Peoples R China

关键词： Viral encephalitis; Neurotropic virus; SARM1; Axonal degeneration; Neuropathology; Brain inflammation

期刊名称：JOURNAL OF NEUROINFLAMMATION （ 影响因子：10.1； 五年影响因子：10.9 ）

ISSN：

年卷期： 2025 年 22 卷 1 期

页码：

收录情况： SCI

摘要： Viral encephalitis, resulting from neurotropic viral infections, leads to severe neurological impairment, inflammation, and exhibits high mortality rates with poor prognosis. Currently, there is a lack of effective targeted treatments for this disease, which poses a significant public health concern. SARM1 has been identified as the pivotal mediator of axonal degeneration and inflammation across various neuropathies, activated by an elevation in the NMN/NAD+ ratio. However, comprehensive in vivo investigations into the role of SARM1-mediated pathogenesis in viral encephalitis are still lacking. In this study, we established mouse models of viral encephalitis using Japanese encephalitis virus (JEV), herpes simplex virus-1 (HSV-1), and rabies virus (RABV) as representative pathogens. Our findings demonstrate that neurotropic virus infections elicit robust axonal degeneration, mitochondrial dysfunction, and profound neuropathological damage in cortical neurons via the activation of SARM1. In mouse models of viral encephalitis, deletion or inhibition of SARM1 effectively preserved axonal morphology and maintained mitochondrial homeostasis, while also attenuating the infiltration of CD45+ leukocytes in the cortex. Consequently, these interventions ameliorated neuropathological damage and enhanced survival outcomes in mice. Our findings suggest that SARM1-mediated axonal degeneration and brain inflammation exacerbate the pathological progression of viral encephalitis. Therapies targeting SARM1 emerge as viable and promising strategies for protecting neuronal function in the context of neurotropic viral infections.

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