State Key Laboratory of Biomacromolecules; Institute of Biophysics; Chinese Academy of Sciences; Beijing, China.
Autophagy. 2013 Aug;9(8):1258-62. doi: 10.4161/auto.24856. Epub 2013 May 14.
Autophagy activity is essential for the survival of neural cells. Impairment of autophagy has been implicated in the pathogenesis of neurodegenerative disorders. Unlike the massive neuron loss in mice deficient for autophagy genes essential for autophagosome formation, we demonstrated that mice deficient for the metazoan-specific autophagy gene Epg5 develop selective neuronal damage and exhibit key characteristics of amyotrophic lateral sclerosis. Epg5 deficiency blocks the maturation of autophagosomes into degradative autolysosomes, slows endocytic degradation and also impairs endocytic recycling. Recessive mutations in human EPG5 have recently been causally associated with the multisystem disorder Vici syndrome. Here we show that while Epg5 knockout mice display some features of Vici syndrome, many phenotypes are absent.
自噬活性对于神经细胞的存活至关重要。自噬功能的损伤与神经退行性疾病的发病机制有关。与自噬基因缺失导致大量神经元丢失的小鼠不同，这些基因对于自噬小体的形成是必需的，我们证明了，后生动物特异性自噬基因 Epg5 缺失的小鼠会出现选择性神经元损伤，并表现出肌萎缩侧索硬化症的关键特征。Epg5 缺失会阻止自噬体成熟为降解性自溶体，从而减缓内吞作用的降解，并损害内吞作用的回收。人类 EPG5 的隐性突变最近与多系统疾病 Vici 综合征有关。在这里，我们表明，尽管 Epg5 敲除小鼠表现出 Vici 综合征的一些特征，但许多表型并不存在。
