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Pathogens 2017, 6(4), 58;

The Role of the Mammalian Prion Protein in the Control of Sleep

The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush Veterinary Centre, Edinburgh EH25 9RG, UK
School of Chemistry, Joseph Banks Laboratories, University of Lincoln, Green Lane, Lincoln, Lincolnshire LN6 7DL, UK
Author to whom correspondence should be addressed.
Received: 28 September 2017 / Revised: 8 November 2017 / Accepted: 13 November 2017 / Published: 17 November 2017
(This article belongs to the Special Issue PrPSc prions: state of the art)
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Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the “eponymous” fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrPC), the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease. Although severe disruption to the circadian rhythm and melatonin release is evident during the pathogenic phases of some prion diseases, untangling whether PrPC plays a role in circadian rhythmicity, as suggested in mice deficient for PrPC expression, is challenging given the lack of basic experimental research. We provide a short review of the small amount of direct literature focused on the role of PrPC in melatonin and circadian rhythm regulation, as well as suggesting mechanisms by which PrPC might exert influence upon noradrenergic and dopaminergic signaling and melatonin synthesis. Future research in this area should focus upon isolating the points of dysfunction within the retino-pineal pathway and further investigate PrPC mediation of pinealocyte GPCR activity. View Full-Text
Keywords: prion; sleep; circadian rhythm; melatonin; serotonin prion; sleep; circadian rhythm; melatonin; serotonin

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Roguski, A.; Gill, A.C. The Role of the Mammalian Prion Protein in the Control of Sleep. Pathogens 2017, 6, 58.

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