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帕金森病中的铁死亡与细胞死亡机制

Ferroptosis and cell death mechanisms in Parkinson's disease.

作者信息

Guiney Stephanie J, Adlard Paul A, Bush Ashley I, Finkelstein David I, Ayton Scott

机构信息

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, Victoria 3052, Australia.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, Victoria 3052, Australia.

出版信息

Neurochem Int. 2017 Mar;104:34-48. doi: 10.1016/j.neuint.2017.01.004. Epub 2017 Jan 9.

Abstract

Symptoms of Parkinson's disease arise due to neuronal loss in multiple brain regions, especially dopaminergic neurons in the substantia nigra pars compacta. Current therapies aim to restore dopamine levels in the brain, but while these provide symptomatic benefit, they do not prevent ongoing neurodegeneration. Preventing neuronal death is a major strategy for disease-modifying therapies; however, while many pathogenic factors have been identified, it is currently unknown how neurons die in the disease. Ferroptosis, a recently identified iron-dependent cell death pathway, involves several molecular events that have previously been implicated in PD. This review will discuss ferroptosis and other cell death pathways implicated in PD neurodegeneration, with a focus on the potential to therapeutically target these pathways to slow the progression of this disease.

摘要

帕金森病的症状是由于多个脑区的神经元丧失所致,尤其是黑质致密部的多巴胺能神经元。目前的治疗旨在恢复大脑中的多巴胺水平,虽然这些治疗能带来症状改善,但并不能阻止进行性神经退行性变。预防神经元死亡是疾病修饰疗法的主要策略;然而,虽然已经确定了许多致病因素,但目前尚不清楚神经元在该疾病中是如何死亡的。铁死亡是最近发现的一种铁依赖性细胞死亡途径,涉及一些先前与帕金森病相关的分子事件。本综述将讨论铁死亡以及与帕金森病神经退行性变相关的其他细胞死亡途径,重点关注治疗性靶向这些途径以减缓该疾病进展的潜力。

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