| Parkinson’s disease(PD)is a common neurodegenerative disorder and its incidence of neurodegenerative diseases ranks second only to Alzheimer’s disease(AD).The main pathological feature of Parkinson’s disease patients is the selective and progressive loss of dopaminergic neurons in the substantia nigra and the presence of intracytoplasmic inclusions(Lewy bodies,LBs)and dystrophic neurites(Lewy neurites,LNs).The aggregated α-synuclein(α-Syn)is a major constituent of LBs and LNs.Proteinaceous depositions of alpha-synuclein(α-syn)and its mutations,A30 P and A53 T,are the main pathological characteristics of PD.What mechanisms or signaling pathways that initiate the production of toxic molecular species of α-synuclein remains obscure.Dendritic cell factor 1(dcf1)is a membrane protein that plays important roles in nerve development in mouse.In our study,we aimed to show that dcf1 overexpression in a PD Drosophila model significantly ameliorates impaired locomotor behavior in third instar larvae and normalizes neuromuscular junction growth.Furthermore,the lifespan dramatically extended by an average of approximately 23%,and climbing ability also significantly increased in adult PD Drosophila expressing dcf1.Surprisingly,dcf1 could prevent α-syn-induced DA neuron loss by aggregating α-syn in the dorsomedial region of Drosophila.Mechanistically,we found and confirmed both dcf1 expressing in Hek293 t cells and its purified protein accelerate alpha-synuclein degradation 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. |
