摘要
阿尔茨海默病(Alzheimer's disease,AD)作为一种典型的神经退行性疾病,其病理机制涵盖了多层次的生物学过程。在中枢神经系统中,离子通道作为关键的细胞结构,对调控神经元兴奋性、突触传递以及神经递质的释放至关重要。现有研究已充分揭示,离子通道在AD中的表达与功能存在显著变化,这些变化不仅涉及Aβ的异常沉积、神经炎症和氧化应激等病理生理过程,还深刻影响了钙稳态以及神经网络的功能。本文系统综述了离子通道在AD发生、发展过程中的关键作用及其潜在机制,深入探讨了这些通道异常如何参与AD的病理过程。同时,本文还分析了离子通道调节在AD治疗中的潜在益处,强调了针对AD多因素性质和亚型异质性的重要性,并提出了多靶点药物研发和精准化治疗作为未来研究方向的合理性。
Alzheimer's disease(AD),a prototypical neurodegenerative disorder,encompasses multifaceted pathological processes.As pivotal cellular structures within the central nervous system,ion channels play critical roles in regulating neuronal excitability,synaptic transmission,and neurotransmitter release.Extensive research has revealed significant alterations in the expression and function of ion channels in AD,implicating an important role of ion channels in the pathogenesis of abnormal Aβdeposition,neuroinflammation,oxidative stress,and disruptions in calcium homeostasis and neural network functionality.This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD,highlighting how these channel abnormalities contribute to AD pathophysiology.We also discuss the therapeutic potential of ion channel modulation in AD treatment,emphasizing the importance of addressing multifactorial nature and heterogeneity of AD.The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
作者
黄冰
杨成敏
陆志成
唐丽娜
莫圣龙
简崇东
商敬伟
HUANG Bing;YANG Cheng-Min;LU Zhi-Cheng;TANG Li-Na;MO Sheng-Long;JIAN Chong-Dong;SHANG Jing-Wei(Graduate School of Youjiang Medical University for Nationalities,Baise 533000,China;Department of Neurology,the Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,China;Key Laboratory of Metabolic Diseases in Baise City,Baise 533000,China)
出处
《生理学报》
北大核心
2025年第2期327-344,共18页
Acta Physiologica Sinica
基金
supported by the National Natural Science Foundation of China(No.82160254)
the High-level Talent Scientific Research Projects of the Affiliated Hospital of Youjiang Medical University for Nationalities(No.R20213001)
the Baise City Scientific Research and Technology Development Program(No.Baike 20224117).
关键词
阿尔茨海默病
治疗策略
离子通道调节
多靶点药物
精准化治疗
Alzheimer's disease
therapeutic strategies
ion channel modulation
multi-target drugs
precision medicine
