Degradation of alpha-synuclein by dendritic cell factor 1 delays neurodegeneration and extends lifespan in Drosophila.
Degradation of alpha-synuclein by dendritic cell factor 1 delays neurodegeneration and extends lifespan in Drosophila.
复制标题
树突状细胞因子 1 对 α-突触核蛋白的降解可延缓果蝇的神经变性并延长寿命。
DOI：
10.1016/j.neurobiolaging.2018.03.010
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Tieqiao Wen
中科院分区：
文献类型：
--
作者：
Shiqing Zhang;Ruili Feng;Yanhui Li;Linhua Gan;Fangfang Zhou;Shiquan Meng;Qian Li;Tieqiao Wen
Parkinson's disease (PD) is a common neurodegenerative disease associated with the progressive loss of dopaminergic neurons in the substantia nigra. Proteinaceous depositions of alpha-synuclein (α-syn) and its mutations, A30P and A53T, are one important characteristic of PD. However, little is known about their aggregation and degradation mechanisms. Dendritic cell factor 1 (DCF1) is a membrane protein that plays important roles in nerve development in mouse. In this study, we aimed to show that DCF1 overexpression in a PDDrosophilamodel significantly ameliorates impaired locomotor behavior in third instar larvae and normalizes neuromuscular junction growth. Furthermore, climbing ability also significantly increased in adult PDDrosophila. More importantly, the lifespan dramatically extended by an average of approximately 23%, and surprisingly, DCF1 could prevent α-syn–induced dopaminergic neuron loss by aggregating α-syn in the dorsomedial region ofDrosophila. Mechanistically, we confirmed that DCF1 could degrade α-syn both in vivo and in vitro. Our findings revealed an important role of DCF1 in PD process and may provide new potential strategies for developing drugs to treat neurodegenerative diseases.
