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神经退行性疾病发病机制中的一氧化氮/一氧化氮合酶系统——综述

Nitric Oxide/Nitric Oxide Synthase System in the Pathogenesis of Neurodegenerative Disorders-An Overview.

作者信息

Iova Olga-Maria, Marin Gheorghe-Eduard, Lazar Izabella, Stanescu Ioana, Dogaru Gabriela, Nicula Cristina Ariadna, Bulboacă Adriana Elena

机构信息

Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania.

Department of Neurology, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

出版信息

Antioxidants (Basel). 2023 Mar 20;12(3):753. doi: 10.3390/antiox12030753.

Abstract

Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of its metabolism, mainly the upregulation of nitric oxide production, has been proposed as a trigger and/or aggravator for many neurological affections. Increasing evidence supports the implication of this molecule in prevalent neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis. The mechanisms proposed for its neurotoxicity mainly center around the increased quantities of nitric oxide that are produced in the brain, their cause, and, most importantly, the pathological metabolic cascades created. These cascades lead to the formation of neuronal toxic substances that impair the neurons' function and structure on multiple levels. The purpose of this review is to present the main causes of increased pathological production, as well as the most important pathophysiological mechanisms triggered by nitric oxide, mechanisms that could help explain a part of the complex picture of neurodegenerative diseases and help develop targeted therapies.

摘要

一氧化氮是一种在自然界中普遍存在的分子,如众多先前研究所示,它是许多重要且有益的分子途径中的关键分子,在中枢神经系统功能中发挥着既定作用。其代谢失调,主要是一氧化氮生成的上调,已被认为是许多神经疾病的触发因素和/或加重因素。越来越多的证据支持该分子与帕金森病、阿尔茨海默病或肌萎缩侧索硬化症等常见神经退行性疾病有关。其神经毒性的机制主要围绕大脑中产生的一氧化氮数量增加、其成因,以及最重要的是由此产生的病理代谢级联反应。这些级联反应导致神经元毒性物质的形成,这些物质在多个层面损害神经元的功能和结构。本综述的目的是介绍病理性生成增加的主要原因,以及一氧化氮引发的最重要的病理生理机制,这些机制有助于解释神经退行性疾病复杂情况的一部分,并有助于开发靶向治疗方法。

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