Tremendous progress has been made to develop the therapy of Alzheimer's disease (AD). Existing several anti-AD remedies, with certain limitations, are far from adequate. Evidence suggests that dihydroergocristine (DHEC) mesylate, one of the main components of Ergoloid mesylates, can reduce the production of amyloid-β in vitro. However, the therapeutic effect of DHEC mesylate in AD and its underlying mechanism are still largely unknown. Herein, we characterized the pharmacological effect of DHEC mesylate in AD and found that the spatial memory disorders and Alzheimer-type pathologies were alleviated by DHEC mesylate administration. Moreover, we demonstrated that DHEC mesylate improved aberrant bisecting N-glycosylation, which was identified as a potential biomarker of AD. We further explored the underlying mechanism and confirmed that DHEC mesylate protected against AD via AMPK and ERK signaling, in which, AMPK was the dominant down-stream molecule of DHEC mesylate. In summary, our findings provide foundations for development of DHEC mesylate as a therapeutic approach for AD.

中文翻译：

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DHEC 甲磺酸盐可减轻阿尔茨海默病模型中的病理和异常二等分 N-糖基化

阿尔茨海默氏病（AD）的治疗方法已取得巨大进展。现有的几种抗 AD 疗法存在一定局限性，远远不够。有证据表明，甲磺酸麦角新碱 (DHEC) 是甲磺酸麦角碱的主要成分之一，可在体外减少β淀粉样蛋白的产生。然而，甲磺酸DHEC对AD的治疗作用及其潜在机制仍不清楚。在此，我们表征了 DHEC 甲磺酸盐在 AD 中的药理作用，发现给予 DHEC 甲磺酸盐可以缓解空间记忆障碍和阿尔茨海默型病理。此外，我们证明 DHEC 甲磺酸盐改善了异常的平分 N-糖基化，这被确定为 AD 的潜在生物标志物。我们进一步探讨了其潜在机制，并证实DHEC甲磺酸盐通过AMPK和ERK信号传导预防AD，其中AMPK是DHEC甲磺酸盐的主要下游分子。总之，我们的研究结果为开发 DHEC 甲磺酸盐作为 AD 治疗方法奠定了基础。