Therapeutic implications of circadian clocks in neurodegenerative diseases

Circadian clocks, endogenous oscillators generating daily biological rhythms, have important roles in the nervous system to control diverse cellular processes—not only in the suprachiasmatic nucleus (SCN), where the master clocks reside to synchronize all circadian clocks in the body but also in other non-SCN areas. Accumulating evidence has shown relationships between circadian abnormalities (e.g., sleep disturbances and abnormal rest–activity rhythms) and disease progressions in various neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's (PD) disease. Although circadian abnormalities were frequently considered as consequences of disease onsets, recent studies suggest altered circadian clocks as risk factors to develop neurodegenerative diseases via altered production or clearance rates of toxic metabolites like amyloid β. In this review, we will summarize circadian clock-related pathologies in the most common neurodegenerative diseases in the central nervous system, AD and PD. Then, we will introduce the current clinical trials to rescue circadian abnormalities in AD and PD patients. Finally, a discussion about how to improve targeting circadian clocks to increase treatment efficiencies and specificities will be followed. This discussion will provide insight into circadian clocks as potential therapeutic targets to attenuate onsets and progressions of neurodegenerative diseases.