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Research Article

AAV9-coGLB1能改善溶酶体储存并恢复GM1神经节苷脂病突变小鼠模型的中枢神经系统炎症

卷 22, 期 4, 2022

发表于: 01 April, 2022

页: [352 - 365] 页: 14

弟呕挨: 10.2174/1566523222666220304092732

价格: $65

摘要

背景:GM1神经节苷脂症（GM1 gangliosidosis ,GM1）是一种常染色体隐性遗传病，其特征是缺乏β-半乳糖苷酶（β-gal），这是一种普遍存在的催化GM1神经节苷脂水解的溶酶体酶。 目的:探讨AAV9-coGLB1在GM1神经节沉积症突变小鼠模型中的有效治疗作用。 方法:设计表达β-gal（AAV9- coGLB1）的新型腺相关病毒9（adeno-associated virus 9, AAV9）载体，用于治疗GM1神经节沉积症。该载体在4周龄时通过尾静脉注射，在Glb1G455R/G455R突变小鼠（GM1小鼠）中广泛和持续表达β-gal达32周。 结果:β-gal水平升高可减轻GM1小鼠的病理损伤。组织学分析显示，AAV9-coGLB1处理小鼠大脑皮质区髓鞘缺损和神经元特异性病理减少。免疫组化染色显示基因治疗后GM1神经节苷脂的积累也减少。这些区域的储存减少伴随着活化小胶质细胞的减少。此外，AAV9治疗逆转了GM1小鼠自噬通量的封锁。 结论:AAV9-coGLB1可减轻小鼠GM1神经节沉积症的病理体征。

关键词: GM1神经节沉积症，小鼠模型，基因治疗，AAV9，中枢神经系统炎症，自噬通量。

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