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神经退行性疾病中的自噬:从致病功能障碍到治疗调节。

Autophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation.

机构信息

Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain; Autonomous University of Barcelona, Barcelona, Spain.

出版信息

Semin Cell Dev Biol. 2015 Apr;40:115-26. doi: 10.1016/j.semcdb.2015.03.005. Epub 2015 Apr 2.

Abstract

Neuronal homeostasis depends on the proper functioning of quality control systems like autophagy. This mechanism is responsible of the clearance of misfolded proteins, aggregates and the turnover of organelles within the neuron. Autophagic dysfunction has been described in many neurodegenerative diseases. It can occur at several steps of the autophagic machinery and can contribute to the formation of intracellular aggregates and ultimately to neuronal death. Accordingly restoring autophagy activity in affected neurons can be an attractive therapeutic approach to fight neurodegeneration. In this review we summarize the present encouraging strategies that have been achieved with pharmacological and genetic treatments aimed to induce neuronal autophagy in experimental models of neurodegenerative diseases.

摘要

神经元的内稳态依赖于质量控制系统的正常运作,如自噬。这个机制负责清除错误折叠的蛋白质、聚集体和神经元内细胞器的更新。自噬功能障碍在许多神经退行性疾病中都有描述。它可能发生在自噬机制的几个步骤中,并有助于形成细胞内聚集体,最终导致神经元死亡。因此,恢复受影响神经元的自噬活性可能是一种有吸引力的治疗神经退行性变的方法。在这篇综述中,我们总结了目前通过药理学和遗传学治疗在神经退行性疾病的实验模型中诱导神经元自噬所取得的令人鼓舞的策略。

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