帕金森病（PD）是世界发病率居第二位的神经退变疾病，研究发现自噬在PD的发病机制中起到重要作用，但调控自噬的信号通路并没有完全阐明。我们的前期研究首次发现TMEM230-A110T可能是PD的致病突变。将TMEM230-A110T转染至SH-SY5Y细胞后细胞自噬和凋亡水平明显增加，伴随p-Erk1/2以及Beclin-1表达上调，但不伴mTOR、P38、JNK水平的变化。因此TMEM230可能是通过Erk1/2/Beclin-1通路调控自噬进而介导神经元退变。本研究将以TMEM230/Erk1/2/Beclin-1为切入点，通过建立TMEM230-A110T转基因小鼠模型、分离原代小鼠黑质多巴胺能神经细胞，从体内、体外两个层面阐明TMEM230通过Erk1/2/Beclin-1通路调控自噬介导神经元退变的机制。本研究有望为研究PD的发病机制以及临床治疗PD提供新的思路和靶点。

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Studies have found that autophagy plays an important role in the pathogenesis of PD, but the signaling pathway regulating autophagy has not been fully clarified. Our study is the first to find that TMEM230-A110T may be the pathogenic mutation of PD. After transfection of TMEM230-A110T into SH-SY5Y cells, autophagy and apoptosis levels were significantly increased, accompanied by up-regulation of p-Erk1/2 and beclin-1 expression without alterating levels of mTOR,P38,JNK . Therefore, TMEM230-A110T may regulate autophagy by Erk1/2/Beclin-1 pathway.By establishing TMEM230-A110T transgenic mouse model,isolating dopaminergic neurons from the mouse nigra, the present study will clarify the mechanism TMEM230 regulated autophagy through Erk1/2/beclin-1 pathway in vivo and in vitro.This study is expected to provide new ideas and targets for the study of the pathogenesis of PD and the clinical treatment of PD.