Circadian Clock Regulates Inflammation and the Development of Neurodegeneration

Abstract

The circadian clock regulates numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of circadian clock machinery influences key activities involved in immune response and brain function. Moreover, Immune activation has been closely linked to neurodegeneration. Here, we review the molecular clock machinery and the diurnal variation of immune activity. We summarize the circadian control of immunity in both central and peripheral immune cells, as well as the circadian regulation of brain cells that are implicated in neurodegeneration. We explore the important role of systemic inflammation on neurodegeneration. The circadian clock modulates cellular metabolism, which could be a mechanism underlying circadian control. We also discuss the circadian interventions implicated in inflammation and neurodegeneration. Targeting circadian clocks could be a potential strategy for the prevention and treatment of inflammation and neurodegenerative diseases.

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

“…Indeed, NR1D1 /Rev-Erbα negatively regulates the expression of circadian clock proteins. Evidence has been provided for relationships between the circadian rhythm and function of the vascular system [ 25 ], and for association of circadian disruption with immune activation–neurodegeneration [ 26 ] and increased incidence of MS [ 24 ]. The NR1D1 5′UTR rs17616365 is associated in brain and arterial tissues with the mRNA levels of CASC3, a protein found to participate to a regulatory network in MS [ 77 ].…”

“…Indeed, recent evidence suggests the role of molecular clocks in regulating blood–brain barrier [ 23 ], in dictating the response of immune pathways, and in modulating innate and adaptive immune crosstalk in autoimmune diseases [ 24 ]. Data support the relationships between the circadian rhythm and function of the vascular system [ 25 ], association of circadian disruption with immune activation–neurodegeneration [ 26 ], and increased incidence of MS [ 24 ].…”

Diurnal Interplay between Epithelium Physiology and Gut Microbiota as a Metronome for Orchestrating Immune and Metabolic Homeostasis

“…A third level of regulation is governed by Dbp and the bZIP transcription factor NFIL3 (nuclear factor interleukin-3-regulated), which regulates Per expression by activation or inhibition. These clock genes, once expressed, regulate the expression of other genes that directly control biological processes; these are termed the clock-controlled genes (CCGs) [ 5 ]. Bmal1 expression is controlled by a positive and a negative loop in intestinal epithelial cells induced by NFIL3 and SIRT1, respectively.…”

Using Microbiome-Based Approaches to Deprogram Chronic Disorders and Extend the Healthspan Following Adverse Childhood Experiences

“…Table 5 [123][124][125][126][127][128][129][130][131][132][133][134][135][136] illustrates examples of NCDs and other disorders that are intimately connected to a disruption in circadian rhythms. Because of the tight interconnects that exist between the circadian clock, the microbiome and systems biology homeostasis or dysbiosis, it is sometimes difficult to distinguish what elements are actually the penultimate controllers.…”