神经毒性反应性星细胞通过和脂质诱导细胞死亡
Kevin A Guttenplan1,2, Maya K Weigel1, Priya Prakash3
1Department of Neurobiology, Stanford University, Stanford, CA, USA.
Nature
|October 7, 2021
概括
星球细胞可以通过和脂质而不是蛋白质杀死中枢神经系统的神经元. 在星球细胞中抑制和脂质合成可以在体外和体内降低这种毒性.
科学领域:
- 神经科学
- 细胞生物学
- 生物化学
背景情况:
- 星细胞在中枢神经系统对损伤和疾病的反应中起着至关重要的作用.
- 据推测,神经细胞在神经退行性疾病中积极导致神经元死亡.
- 鉴定导致神经细胞中介性神经毒性的特定因素是一个持续的挑战.
研究的目的:
- 隔离和识别来自星球细胞的毒性因素的关键组成部分.
- 阐明神经细胞诱导神经元毒性的机制.
- 调查针对星球细胞中介毒性的治疗潜力.
主要方法:
- 开发了一种方法来分离来自星球细胞的有毒因子.
- 使用体外细胞培养系统来评估星球细胞中介毒性.
- 使用急性轴突损伤的体内模型来评估发现的生物相关性.
- 基因改造的星球细胞对ELOVL1酶进行了特别的淘汰,这是和脂质合成中的关键酶.
主要成果:
- 在APOE和APOJ脂质颗粒中确定和脂质作为星体诱导毒性的媒介,而不是蛋白质.
- 证明了在体外显著减轻了天体细胞特异性ELOVL1的毒性.
- 在急性轴突损伤的体内模型中,通过ELOVL1淘汰抑制和脂质形成可降低毒性.
结论:
- 在中枢神经系统中由星细胞衍生的毒性是由和脂质介导的,而不是蛋白质.
- 针对和脂质的合成,特别是通过像ELOVL1这样的酶,提供了一种潜在的治疗策略,以减少星球细胞介导的神经毒性.
- 这些发现揭示了中枢神经系统中由天体细胞引起的细胞死亡的新机制.
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