Circadian clock disruption in neurodegenerative diseases: cause and effect?

Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.