Cystamine and intrabody co-treatment confers additional benefits in a fly model of Huntington's disease
Cystamine and intrabody co-treatment confers additional benefits in a fly model of Huntington's disease
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DOI：
10.1016/j.nbd.2010.04.007
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发表时间：
2010-10-01
影响因子：
6.1
通讯作者：
Wolfgang, W. J.
中科院分区：
文献类型：
--
作者：
Bortvedt, S. F.;McLear, J. A.;Wolfgang, W. J.
亨廷顿氏病（HD）是由亨廷顿基因（HIT）中的多聚谷氨酰胺重复序列的扩增引起的致死性神经退行性疾病，导致突变蛋白质错误折叠、聚集和神经元死亡。喂食果蝇HD模型胱胺，或在神经系统中表达编码抗htt细胞内抗体（胞内抗体）C4-scFy的转基因，证明了治疗潜力，但病理学抑制不完全。我们假设，需要药物和胞内抗体给药的组合方法可以增强对苍蝇HD病理的挽救，并且治疗时间会影响结果。给表达胞内抗体的成年HD果蝇喂食胱胺导致感光细胞神经变性的显著额外拯救，但在寿命方面没有额外的益处。在幼虫和成虫阶段喂食胱胺产生匡威的结果：寿命显着提高，但增加感光细胞的生存。我们得出结论，胱胺胞内抗体联合治疗可以是有效的，减少神经退行性变和延长生存期，这取决于管理协议。(C)2010年爱思唯尔公司All rights reserved.
Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HIT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFy in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete. We hypothesized that a combinatorial approach entailing drug and intrabody administration could enhance rescue of HD pathology in flies and that timing of treatment would affect outcomes. Feeding cystamine to adult HD flies expressing the intrabody resulted in a significant, additional rescue of photoreceptor neurodegeneration, but no additional benefit in longevity. Feeding cystamine during both larval and adult stages produced the converse result: longevity was significantly improved, but increased photoreceptor survival was not. We conclude that cystamine-intrabody combination therapies can be effective, reducing neurodegeneration and prolonging survival, depending on administration protocols. (C) 2010 Elsevier Inc. All rights reserved.