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溶酶体调控在阿尔茨海默病中的新兴作用
郝梦琪1,2,季文博2,古源楷2,卢欣宇2,王莉2,李思琦2,侯阿龙2,高超2,尹又2*
0
(1. 上海理工大学健康科学与工程学院, 上海 200003;
2. 海军军医大学(第二军医大学)第二附属医院神经内科, 上海 200003
*通信作者)
摘要:
阿尔茨海默病(AD)是老年人群体中最常见的神经退行性疾病,其主要病理表现为β淀粉样蛋白沉积形成的老年斑和tau蛋白过度磷酸化形成的神经原纤维缠结。溶酶体是真核细胞中一种重要的细胞器,内含多种水解酶,能分解蛋白质等生物大分子,与胞内运输和自噬密切相关,对维持细胞稳态具有重要意义。本综述总结了溶酶体功能异常与AD发生、发展之间的相互作用关系及调控恢复溶酶体功能在AD治疗中的潜在机制。溶酶体功能失调会导致神经退行性疾病如AD等的发生,调控溶酶体功能是AD一种极具前景的治疗策略,期待未来有更多基于该机制的药物或治疗方案能用于临床治疗AD患者。
关键词:  阿尔茨海默病  溶酶体  纳米药物  小分子药物
DOI:10.16781/j.CN31-2187/R.20240479
投稿时间:2024-07-08修订日期:2024-09-25
基金项目:上海市自然科学基金(22ZR147750),上海市科学技术委员会科技创新行动计划(23Y11906600),海军军医大学第二附属医院创新临床研究项目(2020YLCYJ-Y02).
Emerging role of lysosomal regulation in Alzheimer’s disease
HAO Mengqi1,2,JI Wenbo2,GU Yuankai2,LU Xinyu2,WANG Li2,LI Siqi2,HOU Along2,GAO Chao2,YIN You2*
(1. School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200003, China;
2. Department of Neurology, The Second Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200003, China
*Corresponding author)
Abstract:
Alzheimer’s disease (AD) is the most common neurodegenerative disease in the elderly, and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins. Lysosome is an important organelle in eukaryotic cells, containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules. It is closely related to intracellular transport and autophagy, and is important for maintaining cellular homeostasis. This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes. Lysosomal dysfunction can lead to neurodegenerative diseases such as AD. Modulation of lysosomal function is a promising treatment strategy for AD. It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.
Key words:  Alzheimer’s disease  lysosomes  nanomedicine  small molecule drugs