Functional analysis of atg8 homologues in developing axons

Lc3是唯一已知的自噬体标记物，在发育中的轴突内积累。有趣的是，电子显微镜分析表明，在Lc3聚集区没有诱导自噬，这表明Lc3可能具有除自噬以外的其他特定功能。然而，在Lurcher诱导的神经变性中，细胞内ATP还原和AMPK激活显著地诱导了轴突的自噬。此外，自噬的基因抑制显著加剧了勒彻诱导的神经退化。这些观察强调了自噬在神经退行性变中的细胞保护作用，而自噬途径的修饰和激活可以使我们开发一种新的治疗方法来治疗涉及兴奋性毒性细胞死亡模式的各种神经退行性疾病。

LC3, a only known marker for autophagosomes, were accumulated within developing axons. Interestingly, electron microscopical analysis reveals that there were no induction of autophagy in LC3 accumulated region, indicating that LC3 could have specific functions other than those in autophagy. Whereas, autophagy was remarkably induced in axons by intracellular ATP reduction and AMPK activation in lurcher-induced neurodegeneration. In addition, genetic suppression of autophagy significantly exacerbated Lurcher-induced neurodegeneration. These observations highlighted the cell-protective role of autophagy in neurodegeneration and modification and activation of the autophagic pathway could allow us to develop a new therapeutic approach to various neurodegenerative disorders involving excitotoxic mode of cell death.