D-Methionine 改善空间导航并减轻氧化应激和粉样蛋白病理以特定性别的方式
bioRxiv : the preprint server for biology
|February 9, 2026
概括
口服的D-methionine (D-Met) 改善了空间记忆,并在阿尔茨海默氏症中适度减少了粉样蛋白病理学.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 老年学是一门学科.
背景情况:
- 氧化应激和神经炎症是阿尔茨海默病 (AD) 认知衰退的关键驱动因素.
- 目前的治疗策略通常集中在粉样质斑块上,但需要其他目标.
研究的目的:
- 为了研究口服D-methionine (D-Met) 的作用,一个氧化还原活性氨基酸,在AD病理和小鼠模型的认知功能.
- 为了确定D-Met是否可以减少粉样蛋白负担,脂质过氧化,并提供疾病修饰的好处.
主要方法:
- 患有晚期AD病理的APP/PS1和APPNL-F小鼠被用口服D-Met或载体治疗.
- 行为测试评估了空间学习,记忆和运动活动.
- 生物化学和组织学分析评估了粉样蛋白负担,脂质过氧化,外周标记物和微质表型.
主要成果:
- 在APP/PS1小鼠和雌性NL-F小鼠的两种性别中,D-Methionine改善了空间记忆,在雄性NL-F小鼠中提高了学习能力.
- 观察到粉样蛋白病理的适度,区域特异性减少,同时在雌性APPNL-F小鼠中降低了脂质过氧化.
- D-Met诱导了取决于性别的外周代谢和炎症变化,并重塑了海马的微质特征,特别是在雌性APPNL-F小鼠中.
结论:
- 短期服用D-氨酸作为代谢和氧化还原调节剂,通过增强的微质功能产生适度的粉样蛋白降低效应.
- D-Met的治疗疗效在很大程度上取决于性别和特定的AD小鼠模型.
- 在雌性APPNL-F小鼠中观察到最实质性的益处,突出了对D-Met治疗的性别特异性反应.
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