Mechanisms linking circadian clocks, sleep, and neurodegeneration.

1. Science. 2016 Nov 25;354(6315):1004-1008. doi: 10.1126/science.aah4968. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Musiek ES(1), Holtzman DM(2). Author information: (1)Department of Neurology, Hope Center for Neurological Disorders, and Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA. musieke@neuro.wustl.edu. (2)Department of Neurology, Hope Center for Neurological Disorders, and Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Disruptions of normal circadian rhythms and sleep cycles are consequences of aging and can profoundly affect health. Accumulating evidence indicates that circadian and sleep disturbances, which have long been considered symptoms of many neurodegenerative conditions, may actually drive pathogenesis early in the course of these diseases. In this Review, we explore potential cellular and molecular mechanisms linking circadian dysfunction and sleep loss to neurodegenerative diseases, with a focus on Alzheimer's disease. We examine the interplay between central and peripheral circadian rhythms, circadian clock gene function, and sleep in maintaining brain homeostasis, and discuss therapeutic implications. The circadian clock and sleep can influence a number of key processes involved in neurodegeneration, suggesting that these systems might be manipulated to promote healthy brain aging. Copyright © 2016, American Association for the Advancement of Science. DOI: 10.1126/science.aah4968 PMCID: PMC5219881 PMID: 27885006 [Indexed for MEDLINE]