骨细胞衍生的硬质素在衰老和阿尔茨海默病进展过程中损害了认知功能
Tianshu Shi1,2,3, Siyu Shen1,2,3, Yong Shi1,2,3
1Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, PR China.
Nature metabolism
|February 27, 2024
概括
衰老会增加骨质衍生蛋白质 - - 硬质素,这种蛋白质会穿过血脑屏障,从而损害记忆力. 这一发现揭示了一种新的机制,将骨健康与阿尔茨海默病 (AD) 的进展联系起来.
科学领域:
- 神经生物学 神经生物学 神经生物学
- 内分泌学 在内分泌学.
- 老年学是一门学科.
背景情况:
- 老龄化增加了对神经退行性疾病 (如阿尔茨海默氏症) 的易感性.
- 由骨细胞产生的硬质素抑制了骨的形成,其水平随着年龄的增长而上升.
- Wnt-β-catenin信号传递对记忆和认知功能至关重要.
研究的目的:
- 为了研究骨细胞衍生的硬质素在衰老和病理条件下对认知功能的影响.
- 探索硬质素影响大脑的机制,特别是与阿尔茨海默病相关的机制.
主要方法:
- 在老老鼠身上利用功能增益和功能丧失实验.
- 研究了硬质素穿越血脑屏障的能力.
- 分析了硬质素对Wnt-β-catenin信号传递,突触可塑性和记忆力的影响.
- 研究了AD患者和小鼠模型中的硬质素水平,粉样β (Aβ) 生产和认知障碍之间的关系.
主要成果:
- 骨细胞衍生的硬质素在老年小鼠中穿过血脑屏障,并破坏Wnt-β-catenin信号传递.
- 增加的硬质素水平会损害老年小鼠的突触可塑性和记忆力.
- 斯克莱洛斯通过β-catenin-BACE1信号促进Aβ的产生,使其与AD病原发生有关.
- 高胆固醇水平与人类阿兹海默症患者的严重认知障碍相关.
结论:
- 骨细胞衍生的硬质调解了与衰老和AD认知衰退相关的骨脑交叉声.
- 斯克莱洛斯在增加Aβ生产中的作用突显了它作为阿尔茨海默病治疗点的潜力.
- 向性硬质素可能为打击神经退行和认知障碍提供一种新的治疗策略.
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