negative regulation of circadian rhythm

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of a circadian rhythm behavior. [GOC:go_curators]

Negative regulation of circadian rhythm is a crucial biological process that ensures proper timing and synchronization of physiological functions with the 24-hour day-night cycle. This process involves a complex interplay of molecular mechanisms, including gene expression, protein interactions, and signaling pathways.

**Key components of negative regulation of circadian rhythm:**

* **Transcriptional-translational feedback loop (TTFL):** This loop is the core regulatory mechanism of circadian rhythms. In mammals, the TTFL involves two main transcription factors: CLOCK and BMAL1. These proteins dimerize and activate the transcription of genes encoding PER and CRY proteins. PER and CRY proteins accumulate in the cytoplasm and eventually translocate to the nucleus, where they inhibit the activity of CLOCK/BMAL1, forming a negative feedback loop. This inhibition leads to a decrease in the transcription of PER and CRY genes, ultimately resetting the cycle.

* **Post-translational modifications:** PER and CRY proteins undergo various post-translational modifications, such as phosphorylation and ubiquitination, which modulate their stability, activity, and nuclear localization. These modifications are essential for fine-tuning the timing of the TTFL.

* **Light-dependent signaling:** Light is a powerful synchronizer of circadian rhythms. Light signals are perceived by specialized photoreceptor cells in the retina, which activate a signaling pathway involving the neurotransmitter melatonin. Melatonin can influence the expression of clock genes in the suprachiasmatic nucleus (SCN), the brain's master clock.

* **Other signaling pathways:** Various signaling pathways, including those involving hormones, neurotransmitters, and nutrients, can also modulate circadian rhythms. These pathways can influence the expression of clock genes, post-translational modifications, and other aspects of the TTFL.

**Negative regulation in action:**

* **Synchronization with environmental cues:** Negative regulation allows the circadian clock to synchronize with environmental cues, such as light-dark cycles, ensuring that physiological processes are aligned with the appropriate time of day.

* **Regulation of various physiological processes:** Circadian rhythms influence a wide range of physiological processes, including sleep-wake cycles, hormone secretion, body temperature, and metabolism. Negative regulation ensures that these processes are appropriately timed and coordinated.

* **Maintaining homeostasis:** By coordinating physiological processes, negative regulation of circadian rhythms contributes to overall homeostasis and well-being.

**Disruption of negative regulation:**

Disruption of negative regulation can lead to circadian rhythm disorders, which are associated with various health problems, including sleep disturbances, mood disorders, metabolic disorders, and increased risk of chronic diseases.'
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Proteins (3)

Compounds (1)