神经萎缩作为神经退行性疾病的共同特点，至今尚无上市以其为靶点的药物。神经元中存在活跃的自噬现象，对其正常功能十分重要。课题组前期发现，MAPK信号通路在能量剥夺下，可通过增强自噬发挥神经保护功能，其分子机制尚不清楚。本课题研究的PRAK是MAPK信号通路下游一种主要的压力激活激酶；ARPC2作为Arp2/3复合物的亚单位之一，参与自噬小体的形成。我们前期发现，PRAK在能量剥夺导致的神经萎缩和自噬增强模型中被激活，同时与APRC2的相互作用增强。基于此我们提出假说，在能量剥夺导致神经萎缩模型中，PRAK通过增强与ARPC2的相互作用，继而增强自噬，发挥神经保护作用，并在能量剥夺下动物的学习、记忆等行为中发挥调节作用。我们拟从细胞、动物等多维度探究PRAK与APRC2的相互作用及其在细胞自噬介导的神经萎缩中的功能和机制，拓展非经典自噬内容，为神经退行性疾病的病因提供新的理论基础和治疗思路。

Neuronal atrophy is a common feature in neurodegenerative diseases. However, no effective drugs targeting it have been developed. A growing body of evidence has suggested that autophagy is constitutively activated in healthy neurons, which participates in normal development and signal transduction of neurons. Our previous findings demonstrated that, in addition to the classical PI3K-AKT-mTOR signaling pathway, MAPK signaling pathway also reveals neuroprotective function by enhancing autophagy. It's worth noting that this protective function only occurs in energy deprivation/stress situation, and the molecular mechanism is still unclear. As a protein kinase downstream of MAPK signaling pathway, PRAK is a major stress-activated kinase. Besides, as one of the subunits of Arp2/3 complex, ARPC2 is directly involved in the formation of autophagosomes. Our previous results revealed that PRAK was activated in energy-deprived neuronal atrophy and autophagy enhancement. In addition, the interaction of PRAK and APRC2 was also enhanced in this model. Based on that, we propose hypotheses that PRAK plays a neuroprotective role by enhancing autophagy through interacting with ARPC2 in energy-deprived neuronal atrophy; besides, PRAK plays an important role in the regulation of learning and memory under energy deprivation or stress. Our study intends to reveal the function and mechanism of the interaction between PRAK and APRC2 in the regulation of autophagy-mediated neuronal atrophy in multiple levels, including molecules, cells and animals, which will expand the content of non-classical autophagy. It will also provide the experimental and theoretical basis for clinical researches and new therapeutic strategies for clinical intervention of neurodegenerative diseases.