中国药科大学学报2024,Vol.55Issue(5) :613-623.DOI:10.11665/j.issn.1000-5048.2024040702

基于铁死亡致病机制的抗阿尔茨海默病纳米药物递送系统研究进展

Advances in anti-Alzheimer's disease nano drug delivery system based on pathogenic mechanism of ferroptosis

苏海莹 王钰琨 李维松 周建平 程皓
中国药科大学学报2024,Vol.55Issue(5) :613-623.DOI:10.11665/j.issn.1000-5048.2024040702

基于铁死亡致病机制的抗阿尔茨海默病纳米药物递送系统研究进展

Advances in anti-Alzheimer's disease nano drug delivery system based on pathogenic mechanism of ferroptosis

苏海莹 1王钰琨 1李维松 1周建平 1程皓1
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作者信息

  • 1. 多靶标天然药物全国重点实验室,中国药科大学药学院药剂系,南京 210009
  • 折叠

摘要

铁死亡是一种铁依赖性脂质过氧化和活性氧过度积累诱发的程序性细胞死亡方式,被证明是阿尔茨海默病(Alzheimer's disease,AD)进展过程中神经元死亡的关键病理机制,形成AD致病"铁死亡假说".近年,基于铁死亡致病机制的AD治疗研究主要为脑内铁代谢和微环境氧化还原失衡调控,但血脑屏障及脑内复杂病理环境限制了药物脑内转运、分布及治疗效果,对药物递送技术提出了新要求.本综述在阐述细胞铁死亡过程及其调控机制的基础上,探讨了铁过载和氧化还原失衡与神经元丢失及AD进展的相关性,并基于铁过载和氧化还原失衡综述了抗AD纳米药物递送系统研究进展,为AD治疗和新药研发提供新思路.

Abstract

Ferroptosis,a programmed cell death induced by iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species,is a key pathological mechanism of neuronal death during the progression of Alzheimer's disease(AD),contributing to the formation of"Ferroptosis Hypothesis"for AD pathogenesis.In recent years,there has been extensive research on therapeutic strategies for AD based on the pathogenic mechanism of ferroptosis,focusing primarily on the dysregulation of brain iron metabolism and redox regulation in microenvironment.However,presence of blood-brain barrier and intricate pathological environment within brain impose limitations on intracranial drug transportation,distribution and therapeutic efficacy,thereby necessitating advancements in drug delivery technology.Based on description of ferroptosis process and its regulatory mechanisms,this review explores the association between iron overload and redox imbalance with neuronal loss and AD development,and additionally,summarizes the advancements in nano drug delivery systems targeting iron overload and redox imbalance for potential anti-AD treatments,so as to offer some novel perspectives for AD treatment and drug development.

关键词

阿尔茨海默病/神经元铁死亡/纳米药物递送系统/铁稳态调控/氧化还原调控

Key words

Alzheimer's disease/neuronal ferroptosis/nano drug delivery system/iron homeostasis regulation/redox regulation

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基金项目

国家自然科学基金项目(82404565)

中国博士后科学基金项目(2023M733892)

出版年

2024
中国药科大学学报
中国药科大学

中国药科大学学报

CSTPCD北大核心
影响因子:0.655
ISSN:1000-5048
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