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Current research increasingly indicates the prevalence of sleep\u2013wake 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 \u03b1-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 \u03b1-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\u2013wake disorders triggered by \u03b1-syn mutation and aggregation, thereby providing valuable insights into potential therapeutic avenues for disrupted sleep patterns associated with PD.<\/jats:p>","DOI":"10.1093\/sleep\/zsae297","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T07:22:39Z","timestamp":1734420159000},"source":"Crossref","is-referenced-by-count":7,"title":["Overexpression of \u03b1-synuclein in Pigment Dispersing Factor neurons alters sleep\u2013wake pattern by regulating lipid metabolism in\n                    <i>Drosophila<\/i>"],"prefix":"10.1093","volume":"48","author":[{"given":"Dong","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University , Suzhou ,","place":["China"]},{"name":"Department of Neurology and Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University , Suzhou ,","place":["China"]},{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-9779","authenticated-orcid":false,"given":"Xiang","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key 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