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HCN通道在阿尔茨海默病中作用的研究进展

李晓娟^1,2, 郑铂², 兰平², 张文欣², 李钇朋², 何治^2,3,*

¹三峡大学第二人民医院，宜昌 443000；²三峡大学基础医学院，宜昌 443002；³嘉兴大学医学院，嘉兴 314001

摘要

阿尔茨海默病(Alzheimer's disease, AD)是一种最常见的神经系统退行性疾病，严重影响老年人的记忆、思维和行为。AD标志性的病理特征包括β 淀粉样蛋白(amyloid-β, Aβ)、神经原纤维缠结(neurofibrillary tangles, NFTs)、神经胶质增生和神经元丢失等。超极化激活的环核苷酸门控(hyperpolarization-activated cyclic nucleotide-gated, HCN)通道具有重要的生理功能，特别是在控制静息膜电位、起搏器活动、记忆形成、睡眠和觉醒等方面。本文就HCN通道的结构、分布、调节及其在AD中的作用机制进行综述，以期为AD的预防和治疗提供药物治疗靶点。

关键词： 阿尔茨海默病; HCN通道; 学习与记忆; β淀粉样蛋白

Research progress in the role of HCN channels in Alzheimer's disease

LI Xiao-Juan^1,2, ZHENG Bo², LAN Ping², ZHANG Wen-Xin², Li Yi-Peng², HE Zhi^2,3,*

¹The Second People's Hospital of China Three Gorges University, Yichang 443000, China；²Basic Medical College, China Three Gorges University, Yichang 443002, China；³School of Medical College, Jiaxing University, Jiaxing 314001, China

Abstract

Alzheimer's disease (AD) is the commonest neurodegenerative disease that causes memory decline, cognitive dysfunction and behavior disorders in the aged people. Primary pathological hallmarks of AD include amyloid-β (Aβ), neurofibrillary tangles (NFTs), gliosis, and neuronal loss. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have important physiological functions, especially in aspects of controlling the resting membrane potential, pacemaker activity, memory formation, sleep and arousal. This article reviews the structure, distribution, regulation of HCN channels and the role of HCN channels in the pathological mechanisms of AD, aiming to provide drug therapeutic targets for the prevention and treatment of AD.

Key words: Alzheimer''s disease; HCN channels; learning and memory; amyloid-β (Aβ)

收稿日期：　　录用日期：

通讯作者：何治　　E-mail:

DOI: 10.13294/j.aps.2025.0078

引用本文：

李晓娟, 郑铂, 兰平, 张文欣, 李钇朋, 何治. HCN通道在阿尔茨海默病中作用的研究进展[J]. 生理学报 2025; 77 (5): 867-875.

LI Xiao-Juan, ZHENG Bo, LAN Ping, ZHANG Wen-Xin, Li Yi-Peng, HE Zhi. Research progress in the role of HCN channels in Alzheimer's disease. Acta Physiol Sin 2025; 77 (5): 867-875 (in Chinese with English abstract).