AAV9-mediated gene delivery of MCT1 to oligodendrocytes does not provide a therapeutic benefit in a mouse model of ALS.
AAV9-mediated gene delivery of MCT1 to oligodendrocytes does not provide a therapeutic benefit in a mouse model of ALS.
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AAV9介导的MCT1向少突胶质细胞的基因递送在ALS小鼠模型中不提供治疗益处。
DOI：
10.1016/j.omtm.2021.01.006
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Robberecht W
中科院分区：
文献类型：
--
作者：
Eykens C;Rossaert E;Duqué S;Rué L;Bento-Abreu A;Hersmus N;Lenaerts A;Kerstens A;Corthout N;Munck S;Van Damme P;Holt MG;von Jonquires G;Klugmann M;Van Den Bosch L;Robberecht W
少突胶质细胞功能障碍与肌萎缩侧索硬化症(ALS)的病理生理学有关，ALS是一种以进行性运动神经元丢失为特征的神经退行性疾病。少突胶质细胞提供的营养支持的失败与少突胶质细胞单羧酸转运体1(MCT1)表达的减少有关，并且不利于运动神经元轴突的长期存活。因此，我们建立了一个基于腺相关病毒9(AAV9)的平台，通过该平台MCT1主要针对白质少突胶质细胞，以研究该方法是否可以在ALS的SOD1G93A小鼠模型中提供治疗益处。尽管有良好的少突胶质细胞转导和AAV介导的MCT1转基因表达，但SOD1G93A小鼠的疾病结局没有改变。我们的研究进一步加深了我们目前对ALS中少突胶质细胞病理复杂本质的理解，并为未来有效调节这些细胞的治疗策略的发展提供了有价值的见解。功能障碍的少突胶质细胞参与了ALS运动神经元的变性。Eykens等人。开发了一种基于AAV的方法来刺激SOD1G93A ALS小鼠模型中的少突胶质细胞保护。利用出生后第10天脑室注射AAV9，他们研究了恢复少突胶质细胞蛋白MCT1表达对ALS病理的影响。
Oligodendrocyte dysfunction has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by progressive motor neuron loss. The failure of trophic support provided by oligodendrocytes is associated with a concomitant reduction in oligodendroglial monocarboxylate transporter 1 (MCT1) expression and is detrimental for the long-term survival of motor neuron axons. Therefore, we established an adeno-associated virus 9 (AAV9)-based platform by which MCT1 was targeted mostly to white matter oligodendrocytes to investigate whether this approach could provide a therapeutic benefit in the SOD1G93A mouse model of ALS. Despite good oligodendrocyte transduction and AAV-mediated MCT1 transgene expression, the disease outcome of SOD1G93A mice was not altered. Our study further increases our current understanding about the complex nature of oligodendrocyte pathology in ALS and provides valuable insights into the future development of therapeutic strategies to efficiently modulate these cells. Dysfunctional oligodendrocytes contribute to motor neuron degeneration in ALS. Eykens et al. developed an AAV-based approach to stimulate oligodendrocyte protection in the SOD1G93A ALS mouse model. Using intracerebroventricular AAV9 delivery at postnatal day 10, they investigated the effect of restoring the expression of the oligodendroglial protein MCT1 on ALS pathology.
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
12.7
作者：
Mitew, Stanislaw;Kirkcaldie, Matthew T. K.;Dickson, Tracey C.
通讯作者：
Dickson, Tracey C.
DOI：
10.3791/50326
发表时间：
2013-05-12
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
DeVos SL;Miller TM
通讯作者：
Miller TM
影响因子：
5.3
作者：
Jha MK;Morrison BM
通讯作者：
Morrison BM
影响因子：
25
作者：
Kang, Shin H.;Li, Ying;Fukaya, Masahiro;Lorenzini, Ileana;Cleveland, Don W.;Ostrow, Lyle W.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.