缩醛磷脂在阿尔茨海默病中的研究进展

doi:10.12092/j.issn.1009-2501.2026.09.012

摘要/Abstract

摘要：

阿尔茨海默病（Alzheimer's disease，AD）是一种进行性神经退行性疾病，其发病机制复杂，且目前治疗手段有限，亟需新的干预靶点。缩醛磷脂（plasmalogen）作为一种天然甘油磷脂，广泛存在于细胞膜（如髓鞘）和某些食物（如海鲜）中，其不仅具有显著的抗炎与抗氧化活性，还被证实参与记忆改善。越来越多的证据表明，缩醛磷脂的减少与AD的发生与发展密切相关。缩醛磷脂能够靶向多种关键机制干预AD的病理过程，包括清除β-淀粉样蛋白（β-amyloid，Aβ）沉积、抑制细胞凋亡、促进神经发生和减少小胶质细胞的过度激活，从而发挥神经保护作用。因此补充缩醛磷脂有望成为一种防治AD的新策略。本文旨在总结并探讨缩醛磷脂在AD发病机制与治疗干预中的最新研究进展，以期为AD进一步研究和治疗提供新的方向。

关键词: 阿尔茨海默病, 小胶质细胞, 缩醛磷脂, 脂质

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex pathogenesis and limited current treatment options, urgently requiring new intervention targets. Plasmalogen, a naturally occurring glycerophospholipid, is widely distributed in cell membranes (such as myelin sheaths) and certain foods (such as seafood). Not only do they exhibit significant anti-inflammatory and antioxidant activities, but they have also been demonstrated to participate in memory enhancement. Growing evidence indicates that reduced plasmalogens levels are closely associated with the onset and progression of AD. Plasmalogens can target multiple key mechanisms to intervene in AD pathological processes, including clearing amyloid-β (Aβ) deposits, inhibiting apoptosis, promoting neurogenesis, and reducing excessive activation of microglia, thereby exerting neuroprotective effects. Therefore, supplementing with plasmalogens holds promise as a novel strategy for preventing and treating AD. This article aims to summarize and explore the latest research advances on plasmalogens in AD pathogenesis and therapeutic interventions, with the goal of providing new directions for further AD research and treatment.

Key words: Alzheimer's disease, microglia, plasmalogens, lipid

中图分类号:

金伊楠, 李文静, 边丽华, 郭建友. 缩醛磷脂在阿尔茨海默病中的研究进展[J]. 中国临床药理学与治疗学, 2026, 31(9): 1256-1264.

Yinan JIN, Wenjing LI, Lihua BIAN, Jianyou GUO. Research progress of plasmalogen in Alzheimer's disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(9): 1256-1264.

图/表 2

图 1 缩醛磷脂结构式缩醛磷脂是一类在sn-1位含有特征性乙烯醚键（-O-CH=CH-）的甘油磷脂。sn-2位通常酯化多不饱和脂肪酸（如二十二碳六烯酸，DHA），sn-3位通过磷酸基团（X）连接极性头基，如乙醇胺或胆碱，分别形成缩醛磷脂酰乙醇胺（Pls-Etn）或缩醛磷脂酰胆碱（Pls-Cho）。R1代表sn-1位的烷基链（如棕榈酰基或硬脂酰基）。

Fig.1 Chemical structure of plasmalogens

图 2 缩醛磷脂在阿尔茨海默病中的主要作用机制图2展示了缩醛磷脂通过多条通路干预阿尔茨海默病的核心病理机制。（a）清除Aβ沉积：通过调节α/β-分泌酶活性减少Aβ生成，并直接解聚Aβ纤维；（b）抑制神经元凋亡：激活PI3K/Akt和ERK生存信号，抑制线粒体凋亡途径及p38 MAPK/p75NTR等死亡信号；（c）促进神经发生与突触保护：通过Wnt/β-catenin通路促进海马神经干细胞分化为神经元，并上调BDNF表达增强突触可塑性；（d）缓解神经炎症：抑制小胶质细胞/星形胶质细胞的过度活化，下调GFAP、Iba-1等炎性信号分子。

Fig.2 Major mechanisms of plasmalogens in Alzheimer's disease

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