Nuclear receptors and circadian clock: Implications for inflammatory diseases

Abstract

The biological clock is a set of evolutionarily conserved "clock proteins"that generate circadian rhythms in behavior and physiological processes. The clock programs these processes at specific times of the day, allowing the organism to optimize its functions by anticipating predictable daily changes such as day/night, hence sleep/wake or feeding/ fasting cycles. Modern lifestyle, i.e., exposure to light at night, shift work and irregular eating patterns and sleep schedules desynchronize the clocks residing in each organ. This dissonance is associated with an increased risk of developing various diseases such as cancer, metabolic, cardiovascular and chronic inflammatory diseases. The response to pathogens is circadian due to the rhythmic number and behavior of the immune cells. Thus, there is a rhythmic response to endotoxins and to infection by bacterial and viral pathogens. These oscillations are also observed in symptoms that are generally more severe in the morning in cardiovascular diseases or at night in asthma for example. Chronotherapy, i.e., the administration of a pharmacological compound at the most appropriate time of the day to optimize its efficacy and reduce side effects, has been used for a long time in the treatment of cancers, in particular colorectal cancers. However, it is still little considered in the management of cardiovascular or inflammatory diseases. A better understanding of biological rhythms and/or the targeting of certain clock genes, in particular nuclear receptors, by pharmacological compounds administered at the optimal time of day, represents a promising therapeutic avenue.