帕金森病（Parkinson’s Disease, PD）是目前常见的老年性神经退行性疾病,在病理学上，表现为中脑黑质致密部多巴胺能神经元的变性以及剩余存活神经元中异常蛋白聚集或路易小体的形成。路易小体的主要组成份是α-synuclein。α-synuclein的寡聚化和原纤维生长在PD的发生中起着非常重要的作用。本项目在前期研究的基础中首次发现赖氨酰氧化酶（Lysyl Oxidase，LOX）可能对α-synuclein寡聚体的形成具有调节作用。我们拟通过利用LOX敲除细胞、胚胎干细胞分化的多巴胺能神经元为模型，探讨氧化应激通过调节LOX表达，氧化α-synuclein N端赖氨酸，促进寡聚化形成，从而导致细胞毒性，引起多巴胺能神经元死亡的机制，本项目的顺利实施将有助于扩展对PD发生机制的认识，同时为干预和治疗提供潜在的靶点。

Parkinson's disease (Parkinson's Disease, PD) is a common age-related neurodegenerative diseases characterized by degeneration of dopamine neurons and neuronal survival in the remaining abnormal protein aggregation or formation of Lewy body in the substantia nigra pars compacta. The main ingredient of Lewy body is α-synuclein. α-synuclein oligomerization and fibril growth play central roles in PD development. The this project, on the basis of preliminary studies for the first time found that lysyl oxidase (Lysyl Oxidase, LOX) may reguates α-synuclein oligomerization. Using LOX knockout cells, dopaminergic neurons differentiated from embryonic stem cell, we will investigate the mechanism of LOX expression regulated by oxidative stress. Then, it oxides α-synuclein N-terminal lysine, promotes oligomerization, leading to cell toxic and eventually causing the death of dopaminergic neurons.The successful implementation of this project will contribute to expand understanding of the pathogenesis of PD, while providing potential targets for intervention and treatment.