CD22阻断恢复老化大脑中的恒常性微细胞
John V Pluvinage1,2,3, Michael S Haney3, Benjamin A H Smith1,4,5
1Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|April 5, 2019
概括
研究人员发现, 抑制CD22受体可以恢复老年细胞的排泄能力. 这种干预可以改善老年小鼠的认知功能,
科学领域:
- 神经科学
- 免疫学
- 老龄化研究
背景情况:
- 微细胞对中枢神经系统 (CNS) 稳态至关重要,通过细胞化清除残渣.
- 随着年龄的增长和神经退行性疾病,微细胞的细胞功能下降,与认知能力下降相关.
- 微质功能受损的机制和恢复的认知益处在很大程度上是未知的.
研究的目的:
- 识别与年龄相关的微细胞瘤的遗传修饰者.
- 研究CD22在衰老中的微质功能.
- 评估CD22抑制对认知衰老的治疗潜力.
主要方法:
- 结合CRISPR-Cas9淘汰屏幕和RNA测序来识别遗传修饰物.
- 使用抗体介导的CD22阻断的体内研究.
- 在老鼠中评估各种碎片的微细胞分解.
- 在CD22抑制后对老鼠的认知功能进行评估.
主要成果:
- CD22是一种B细胞受体,被确定为微质细胞灭菌的负调节者,在老年微质细胞中被调节上升.
- CD22调解了α2,6结合的酸对细胞的抑制作用.
- 在体内,CD22抑制增强了髓残留物,粉样β和α-synuclein的清除.
- 在老年小鼠中,长期向中枢神经系统输送抗CD22抗体使小质细胞重编程至同位状态,并改善认知功能.
结论:
- CD22 是与年龄相关的微细胞衰竭的关键调解物.
- 抑制CD22可恢复微质平稳功能,并提高老年人的认知能力.
- 针对CD22为与年龄相关的认知衰退和神经退行提供了一个有前途的治疗策略.
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