Overexpression of α-synuclein in Pigment Dispersing Factor neurons alters sleep–wake pattern by regulating lipid metabolism in Drosophila

• DOI: 10.1093/sleep/zsae297
• Publication Date: 2024-12-21T06:47:23Z
• Authors: Dong Xia; Ying Chen; Xiang Fu; Hui-Yi Liu; Mu-Yan Sun; Fen Wang; Yong Zhang; Chun-Feng Liu; Jun-Yi Liu
• Keywords: Sleep; Nap

Parkinson's disease (PD) is a complex neurodegenerative disorder, characterized by the aggregation of α-synuclein (α-syn). Current research increasingly indicates prevalence sleep-wake disorders in early-stage PD, although underlying pathogenic mechanisms remain unclear. In this study, transgenic Drosophila models were utilized to observe excessive daytime sleepiness and impaired anticipation flies overexpressing α-syn pan-neurons circadian clock neurons. Additionally, deficits projection Pigment Dispersing Factor (PDF) neuron terminals, which are involved sleep rhythm, identified. An imbalance lipid metabolism homeostasis was detected brains mutants. Ultimately, inhibition Sterol Regulatory Element-Binding Protein (SREBP) activity led an improvement reduced duration phenotype. Our results suggest that pathways play role triggered mutation aggregation, thereby providing valuable insights into potential therapeutic avenues for disrupted patterns associated with PD.