Retinoids and motor neuron disease: Potential role in amyotrophic lateral sclerosis.
Retinoids and motor neuron disease: Potential role in amyotrophic lateral sclerosis.
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DOI：
10.1016/j.jns.2015.11.058
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发表时间：
2016-01-15
影响因子：
4.4
通讯作者：
Lafarga M
中科院分区：
文献类型：
--
作者：
Riancho J;Berciano MT;Ruiz-Soto M;Berciano J;Landreth G;Lafarga M
肌萎缩侧索硬化症(ALS)是影响运动神经元的最常见的神经退行性疾病。这种致命的疾病以进行性肌肉萎缩为特征，不幸的是，它没有有效的治疗方法。尽管有一小部分肌萎缩侧索硬化症病例有熟悉的起源，但绝大多数被认为是零星起源。尽管ALS的发病机制尚未完全阐明，但基因表达、蛋白质代谢、轴突运输和神经胶质细胞紊乱等多种细胞功能紊乱与MN变性有关。其中，蛋白质平衡是研究得最多的一种。维甲酸是维生素A衍生的物质，在胚胎发生、发育、细胞程序性死亡和其他细胞功能中发挥着至关重要的作用。维甲酸激动剂在核维甲酸受体的激活过程中发挥转录因子的作用。一些文献报道表明，类维甲酸通过调节泛素-蛋白酶体系统和自噬-溶酶体反应这两条主要途径参与蛋白平衡的调节。此外，有一些证据表明，维甲酸本身在ALS的发病机制中发挥了作用。在这篇综述中，我们讨论了蛋白平衡紊乱作为MN退变的触发因素的重要性和维甲酸调节它的能力，以及维甲酸作为ALS新疗法的潜在治疗作用。
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MN). This fatal disease is characterized by progressive muscular atrophy and unfortunately it does not have an effective treatment. Although a small proportion of ALS cases have a familiar origin, the vast majority of them are thought to have a sporadic origin. Although the pathogenesis of ALS has not been fully elucidated, various disorders in different cellular functions such as gene expression, protein metabolism, axonal transport and glial cell disorders have been linked to MN degeneration. Among them, proteostasis is one of the best studied. Retinoids are vitamin A-derived substances that play a crucial role in embryogenesis, development, programmed cell death and other cellular functions. Retinoid agonists behave as transcription factors throughout the activation of the nuclear retinoid receptors. Several reports in the literature suggest that retinoids are involved in proteostasis regulation, by modulating its two major pathways, the ubiquitin-proteasome system and the autophagy-lysosome response. Additionally, there are some evidences for a role of retinoids themselves, in ALS pathogenesis. In this review, we discuss the importance of proteostasis disruption as a trigger for MN degeneration and the capability of retinoids to modulate it, as well as the potential therapeutic role of retinoids as a new therapy in ALS.
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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