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用新型多功能化合物靶向阿尔茨海默病中的金属失衡和氧化应激。

Targeting Metal Imbalance and Oxidative Stress in Alzheimer's Disease with Novel Multifunctional Compounds.

作者信息

Charissopoulos Eleftherios, Pontiki Eleni

机构信息

Laboratory of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

出版信息

Molecules. 2025 Aug 27;30(17):3512. doi: 10.3390/molecules30173512.

Abstract

Alzheimer's disease (AD) is considered to be one of the most common types of dementia, threatening the health of elderly individuals. Enhancing the brain's cholinergic activity is currently the primary therapeutic strategy for treating AD patients. Acetylcholine and butyrylcholine are key targets in this approach, as they function as neuromodulators within the cerebrum-particularly in its various cholinergic regions responsible for essential functions like memory, thought, inspiration, and excitement. Oxidative stress and free radicals are considered to play a crucial role in the pathogenesis of AD and may be key factors in its etiology. Additionally, oxidants and oxidative stress-induced products can upregulate amyloid precursor protein (APP) expression, promoting Aβ aggregation. Another major factor in the pathogenesis of AD is the imbalance of metal homeostasis in the brain. Notably, the mammalian brain contains significantly higher concentrations of Cu, Zn, and Fe ions compared to other tissues. The present review focuses on novel bifunctional metal chelators with potential antioxidant activity for the treatment of AD.

摘要

阿尔茨海默病(AD)被认为是最常见的痴呆类型之一,威胁着老年人的健康。增强大脑的胆碱能活性是目前治疗AD患者的主要治疗策略。乙酰胆碱和丁酰胆碱是这种方法的关键靶点,因为它们在大脑中作为神经调节剂发挥作用,特别是在其负责记忆、思维、灵感和兴奋等基本功能的各个胆碱能区域。氧化应激和自由基被认为在AD的发病机制中起关键作用,可能是其病因的关键因素。此外,氧化剂和氧化应激诱导的产物可上调淀粉样前体蛋白(APP)的表达,促进Aβ聚集。AD发病机制中的另一个主要因素是大脑中金属稳态的失衡。值得注意的是,与其他组织相比,哺乳动物大脑中铜、锌和铁离子的浓度明显更高。本综述重点关注具有潜在抗氧化活性的新型双功能金属螯合剂在AD治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f817/12430417/c8ff1f7c213d/molecules-30-03512-g001.jpg

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