title: Mechanisms linking circadian clocks, sleep, and neurodegeneration.
abstract: 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.
authors.affiliation: 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.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Musiek
authors.affiliation: Department of Neurology, Hope Center for Neurological Disorders, and Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000502:physiology; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D020920:Dyssomnias / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D051379:Mice; D012890:Sleep; D013493:Suprachiasmatic Nucleus / Q000503:physiopathology