Autophagy and its neuroprotection in neurodegenerative diseases
Autophagy and its neuroprotection in neurodegenerative diseases
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DOI：
10.3969/j.issn.1673-5374.2011.23.001
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发表时间：
2011-08-15
影响因子：
6.1
通讯作者：
Le, Weidong
中科院分区：
文献类型：
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作者：
Gu, Ping;Jakkoju, Avaneesh;Le, Weidong
有人认为蛋白质错误折叠和聚集对神经退行性疾病的发展有重大影响。错误折叠和聚集的蛋白质由泛素蛋白酶体系统 (UPS) 以及微观和宏观自噬溶酶体途径 (ALP) 清除。自噬体功能障碍与越来越多的疾病有关，包括神经退行性疾病。自噬是一种细胞自噬过程，在神经保护以及神经元损伤和死亡中发挥重要作用。虽然自噬活性的降低会干扰蛋白质降解并可能干扰细胞器更新，但在许多疾病模型中，自噬的增加已被证明可以促进易聚集蛋白质的清除并促进神经元存活。另一方面，过多的自噬活性可能是有害的，这表明自噬的调节对于决定细胞命运至关重要。在这篇综述论文中，我们将讨论 ALP 生物学的各个方面及其在神经细胞死亡和存活中的双重功能。我们还将评估自噬在神经退行性疾病中的作用，包括阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症。最后，我们将探索自噬调节剂在几种神经退行性疾病中的治疗潜力。
It has been suggested that protein misfolding and aggregation contribute significantly to the development of neurodegenerative diseases. Misfolded and aggregated proteins are cleared by ubiquitin proteasomal system (UPS) and by both Micro and Macro autophagy lysosomal pathway (ALP). Autophagosomal dysfunction has been implicated in an increasing number of diseases including neurodegenerative diseases. Autophagy is a cellular self-eating process that plays an important role in neuroprotection as well as neuronal injury and death. While a decrease in autophagic activity interferes with protein degradation and possibly organelle turnover, increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival in a number of disease models. On the other hand, too much autophagic activity can be detrimental, suggesting the regulation of autophagy is critical in dictating cell fate. In this review paper, we will discuss various aspects of ALP biology and its dual functions in neuronal cell death and survival. We will also evaluate the role of autophagy in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis. Finally, we will explore the therapeutic potential of autophagy modifiers in several neurodegenerative diseases.