机构：[1]Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China,[2]Department of Neurology and Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University, Suzhou, China,苏州大学附属第二医院[3]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China,[4]Cambridge-Suda Genomic Resource Center, Soochow University, Suzhou, China[5]Department of Neurology, Xiongan Xuanwu Hospital, Xiongan, China神经科系统神经内科首都医科大学宣武医院
Parkinson's disease (PD) is a complex neurodegenerative disorder, characterized by the aggregation of alpha-synuclein (alpha-syn). Current research increasingly indicates the prevalence of sleep-wake disorders in early-stage PD, although the underlying pathogenic mechanisms remain unclear. In this study, transgenic Drosophila models were utilized to observe excessive daytime sleepiness and impaired anticipation in flies overexpressing alpha-syn in pan-neurons and circadian clock neurons. Additionally, deficits in projection of Pigment Dispersing Factor (PDF) neuron terminals, which are involved in Drosophila sleep and circadian rhythm, were identified. An imbalance in lipid metabolism homeostasis was detected in the brains of alpha-syn overexpressing mutants. Ultimately, the inhibition of Sterol Regulatory Element-Binding Protein (SREBP) activity led to an improvement in the reduced daytime sleep duration phenotype. Our results suggest that lipid pathways play a role in sleep-wake disorders triggered by alpha-syn mutation and aggregation, thereby providing valuable insights into potential therapeutic avenues for disrupted sleep patterns associated with PD.
基金：
Suzhou Science, Education and Health Project [KJXW202387]; STI2030-Major Projects [2021ZD0203400]; National Natural Science Foundation of China [32271206]; Science and Technology Innovation Project of Xiongan New Area [2023XAGG0073]; Jiangsu Provincial Medical Key Discipline [ZDXK202217]; Suzhou Key Laboratory [SZS2023015]; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
第一作者机构：[1]Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China,[2]Department of Neurology and Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University, Suzhou, China,[3]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China,
通讯作者：
通讯机构：[2]Department of Neurology and Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University, Suzhou, China,[3]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China,[5]Department of Neurology, Xiongan Xuanwu Hospital, Xiongan, China
推荐引用方式(GB/T 7714)：
Xia Dong,Chen Ying,Fu Xiang,et al.Overexpression of α-synuclein in Pigment Dispersing Factor neurons alters sleep-wake pattern by regulating lipid metabolism in Drosophila[J].SLEEP.2025,48(3):doi:10.1093/sleep/zsae297.
APA：
Xia, Dong,Chen, Ying,Fu, Xiang,Liu, Hui-Yi,Sun, Mu-Yan...&Liu, Jun-Yi.(2025).Overexpression of α-synuclein in Pigment Dispersing Factor neurons alters sleep-wake pattern by regulating lipid metabolism in Drosophila.SLEEP,48,(3)
MLA：
Xia, Dong,et al."Overexpression of α-synuclein in Pigment Dispersing Factor neurons alters sleep-wake pattern by regulating lipid metabolism in Drosophila".SLEEP 48..3(2025)
