Regulation of proteostasis by sleep through autophagy in Drosophila models of Alzheimer's disease.

Autor:	Ortiz-Vega N; https://ror.org/024mw5h28 Department of Neurology, University of Chicago, Chicago, IL, USA.; Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.; Graduate Program in Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA., Lobato AG; https://ror.org/024mw5h28 Department of Neurology, University of Chicago, Chicago, IL, USA., Canic T; Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Physics, University of Miami, Coral Gables, FL, USA., Zhu Y; Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA., Lazopulo S; Department of Physics, University of Miami, Coral Gables, FL, USA., Syed S; Department of Physics, University of Miami, Coral Gables, FL, USA., Zhai RG; https://ror.org/024mw5h28 Department of Neurology, University of Chicago, Chicago, IL, USA rgzhai@uchicago.edu.; Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Sep 05; Vol. 7 (11). Date of Electronic Publication: 2024 Sep 05 (Print Publication: 2024).
DOI:	10.26508/lsa.202402681
Abstrakt:	Sleep and circadian rhythm dysfunctions are common clinical features of Alzheimer's disease (AD). Increasing evidence suggests that in addition to being a symptom, sleep disturbances can also drive the progression of neurodegeneration. Protein aggregation is a pathological hallmark of AD; however, the molecular pathways behind how sleep affects protein homeostasis remain elusive. Here we demonstrate that sleep modulation influences proteostasis and the progression of neurodegeneration in Drosophila models of tauopathy. We show that sleep deprivation enhanced Tau aggregational toxicity resulting in exacerbated synaptic degeneration. In contrast, sleep induction using gaboxadol led to reduced toxic Tau accumulation in neurons as a result of modulated autophagic flux and enhanced clearance of ubiquitinated Tau, suggesting altered protein processing and clearance that resulted in improved synaptic integrity and function. These findings highlight the complex relationship between sleep and regulation of protein homeostasis and the neuroprotective potential of sleep-enhancing therapeutics to slow the progression or delay the onset of neurodegeneration. (© 2024 Ortiz-Vega et al.)
Databáze:	MEDLINE
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