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铜在神经退行性变中的关键作用:神经退行性疾病治疗的新策略。

The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy of Neurodegenerative Disorders.

机构信息

Dipartimento di Farmacia-Scienze del Farmaco , Università degli Studi di Bari Aldo Moro , Via Orabona 4 , 70125 , Bari , Italy.

Biofordrug srl, Dipartimento di Farmacia-Scienze del Farmaco , Università degli Studi di Bari Aldo Moro , Via Orabona 4 , 70125 , Bari , Italy.

出版信息

Mol Pharm. 2018 Mar 5;15(3):808-820. doi: 10.1021/acs.molpharmaceut.7b00841. Epub 2018 Feb 2.

Abstract

Copper is an essential trace element for the human body since it is a cofactor of several enzymes and proteins and plays a pivotal role in several biological functions (e.g., respiration, protection from oxidative damage, iron metabolism, etc.), also including the central nervous system development and functioning (e.g., synthesis of neurotransmitters, myelination, activation of neuropeptides, etc.). Therefore, copper dysmetabolism is associated with different toxic effects, mainly represented by oxidative stress, and it has been reported in many neurodegenerative disorders, such as Wilson's disease, Menkes disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This paper shows a detailed report of how copper is involved in the pathophysiology of these diseases. Moreover, a hint on novel therapeutic approaches based on restoring copper homeostasis through metal chelators will be pointed out.

摘要

铜是人体必需的微量元素,因为它是几种酶和蛋白质的辅助因子,在几种生物功能(如呼吸、防止氧化损伤、铁代谢等)中发挥关键作用,也包括中枢神经系统的发育和功能(如神经递质的合成、髓鞘形成、神经肽的激活等)。因此,铜代谢紊乱与不同的毒性作用有关,主要表现为氧化应激,并且已在许多神经退行性疾病中报道,如威尔逊病、Menkes 病、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。本文详细报告了铜如何参与这些疾病的病理生理学。此外,还将指出通过金属螯合剂恢复铜动态平衡的新型治疗方法的提示。

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