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The autophagy protein Atg9 functions in glia and contributes to parkinsonian symptoms in a Drosophila model of Parkinson's disease

摘要Parkinson's disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation of α-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson's disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson's disease.These results may provide new insights on the underlying mechanism of Parkinson's disease.

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作者 Shuanglong Yi [1] Linfang Wang [1] Margaret S.Ho [2] Shiping Zhang [2] 学术成果认领
作者单位 School of Life Science and Technology,ShanghaiTech University,Shanghai,China;College of Life Sciences,University of Chinese Academy of Sciences,Beijing,China [1] School of Life Science and Technology,ShanghaiTech University,Shanghai,China [2]
DOI 10.4103/1673-5374.382259
发布时间 2023-12-26(万方平台首次上网日期,不代表论文的发表时间)
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中国神经再生研究(英文版)

中国神经再生研究(英文版)

2024年19卷5期

1150-1155页

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