FKBP14 regulates sleep in response to starvation and oxidative stress
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Authors
Robertson, Meagan D.
Issue Date
2013
Type
Thesis
Language
Keywords
fkbp14 , Notch , oxidative stress , presenilin , sleep , starvation
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Abstract
Animals modulate sleep in response to stress that include hypoxia, aging, diet and starvation; however, the molecular basis for integrating stress and sleep remain unclear. As animals age, they experience an increase in oxidative damage and loss of sleep quality. Moreover, both oxidative stress and poor sleep quality contribute to shortened lifespans in Drosophila and other animals. FKBP14 is a member of a highly conserved family of FK506-binding proteins (FKBPs) that bind to the immunosuppressant drug FK506. FKBP14 has recently been identified as a Presenilin (Psn)-dependent mediator of Notch signaling. Psn plays a pivotal role in the formation of Amyloid β (Aβ) plaques that contribute to Alzheimer's disease, and recently sleep loss has been associated with these plaques in the brain. We have identified Fkbp14 as a potent inhibitor of sleep during starvation and found that it is necessary in the peptidergic neurons of the fly brain for this response, suggesting that FKBP14 regulates sleep in the brain during starvation. Oxidative stress also contributes to Aβ plaques and we find that Fkbp14 mutants are resistant to changes in sleep when fed the free-radical inducing drug, Paraquat, which is known to impair sleep quality and shorten lifespan. The possible role of FKBP14 in mediating Notch signaling to regulate sleep in response to oxidative stress exemplifies the importance of sleep quality and may provide insight into age and stress-related perturbations in sleep that contribute to Alzheimer's disease.
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In Copyright(All Rights Reserved)