基础科学和病原发生学
1Alzheimer's Center at Temple, Lewis Katz School of Medicine, Philadelphia, PA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
概括
阿尔茨海默病和病理学将大脑内皮细胞转移到糖解,增加炎症和血脑屏障的透性. 恢复正常的新陈代谢可以扭转这些有害影响,提供新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 大脑内皮细胞 (cEC) 对血脑屏障 (BBB) 完整性和神经血管单元功能至关重要.
- cECs的功能障碍导致神经炎症,神经退行和在阿尔茨海默病 (AD) 和脑粉样血管病变 (CAA) 中观察到的微出血.
- 病理性粉样β (Aβ) 和陶聚合物改变了CEC新陈代谢,促进了糖分解并损害了线粒体功能,这与BBB透性有关.
研究的目的:
- 调查AD和CAA病理改变cEC功能的机制.
- 了解CEC功能障碍如何调解BBB和神经血管变化.
- 探索cECs中的代谢转变与内皮炎症激活和BBB透性之间的联系.
主要方法:
- 使用海马细胞外流量分析仪评估了人类cEC中的线粒体呼吸和糖解.
- 通过使用ECIS Zθ系统通过跨内皮电阻 (TEER) 测量BBB功能.
- 使用MSD V-Plex神经炎症面板,西布洛特和免疫光技术量化内皮炎症激活和血管功能障碍途径.
- 在实验室和脑粉症和陶病病的动物模型中研究了糖解抑制对BBB和神经血管功能障碍的影响.
主要成果:
- 无论是Aβ和tau聚合物,都会诱导cEC中的代谢转向糖解,导致炎症激活和BBB透性.
- 将糖溶解降低到正常水平可以逆转AD病理聚合物引起的有害脑血管影响.
- Aβ直接将cECs从线粒体呼吸转换为糖解,而tau最初会过度激活糖解,导致炎症和BBB透性,随后是线粒体功能障碍和细胞死亡.
- 关键的发现得到了动物模型中大脑粉样性粉症和病的证实.
结论:
- 已经确定了一种新的代谢机制,涉及由Aβ和tau物种介导的内皮炎症激活和BBB病理.
- 针对这种代谢途径为AD,CAA和陶病症提供了潜在的治疗策略.
- 旨在使内皮代谢正常化的干预措施可以限制免疫细胞透和神经退行性疾病中的BBB透性.
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