Background

Despite extensive global efforts, there is currently no effective remedy for Alzheimer’s disease (AD).

Objectives

This investigation aimed to examine the impact of vitamin D/vitamin D receptor (VDR)/ATG16L1 signaling on memory in AD mice, as well as the levels of autophagy and inflammation in the hippocampus.

Results

Administering cholecalciferol cholesterol emulsion (CCE), which serves as a precursor to 1,25-OH vitamin D3, through water feeding for a duration of 12 weeks demonstrated the ability to mitigate both short-term and long-term memory impairments in AD mice. CCE treatment reduced the deposition of TAU protein in the hippocampus, suppressed the phosphorylation of TAU Thr181 and 212, and significantly decreased Aβ (1–40) levels. Moreover, CCE heightened hippocampal autophagy in AD mice, upregulated the expression of ATG16L1 and LC3B, and inhibited P62 expression. In addition, CCE supplementation attenuated hippocampal inflammation in AD mice by decreasing the levels of IL1β and TNFα and restoring the TOM1/IL1R1 pathway. The Luciferase reporter assay verified that the knockdown of VDR could impede the activation of the ATG16L1 promoter by vitamin D, and ChIP analysis confirmed that VDR could bind to the ATG16L1 promoter and exert its function.

Conclusion

CCE exhibits potential in safeguarding hippocampal neurons against AD-induced harm, stimulating autophagy, and suppressing inflammation. These effects may be regulated by VD/VDR/ATG16L1 signaling.

中文翻译：

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VD/VDR 介导的 ATG16L1 激活可减少阿尔茨海默病样病理和认知能力下降

背景

尽管全球做出了广泛的努力，但目前还没有有效的治疗阿尔茨海默病（AD）的方法。

目标

本研究旨在探讨维生素 D/维生素 D 受体 (VDR)/ATG16L1 信号对 AD 小鼠记忆的影响，以及海马体自噬和炎症水平。

结果

通过喂水持续 12 周，给予胆钙化醇胆固醇乳剂 (CCE)（1,25-OH 维生素 D3 的前体），证明能够减轻 AD 小鼠的短期和长期记忆障碍。CCE 治疗减少了海马中 TAU 蛋白的沉积，抑制了 TAU Thr181 和 212 的磷酸化，并显着降低了 Aβ (1-40) 水平。此外，CCE 增强 AD 小鼠海马自噬，上调 ATG16L1 和 LC3B 的表达，并抑制 P62 的表达。此外，CCE 补充剂可通过降低 IL1β 和 TNFα 水平并恢复 TOM1/IL1R1 通路来减轻 AD 小鼠的海马炎症。荧光素酶报告基因实验验证了VDR的敲低可以阻碍维生素D对ATG16L1启动子的激活，ChIP分析证实VDR可以与ATG16L1启动子结合并发挥其功能。

结论

CCE 在保护海马神经元免受 AD 引起的伤害、刺激自噬和抑制炎症方面具有潜力。这些效应可能受到 VD/VDR/ATG16L1 信号传导的调节。