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PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders
PPARalpha as a possible drug target for treating sleep problems tied to body clock disruptions
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Abstract
Circadian locomotor activity was phase-advanced about 3 hours in mice given the PPARalpha ligand bezafibrate under light-dark conditions.
- Bezafibrate advanced the phase of the endogenous clock in mice, demonstrating its influence on circadian rhythms.
- Mice with lesions in the suprachiasmatic nucleus still showed phase advancement after bezafibrate administration, indicating a SCN-independent mechanism.
- Circadian expression of clock genes such as period2, BMAL1, and Rev-erbalpha was phase-advanced in several tissues, including cortex, liver, and fat.
- The drug also advanced the activity phase in model mice with delayed sleep phase syndrome due to a Clock gene mutation.
- Findings suggest that PPARalpha may be a potential target for treating circadian rhythm sleep disorders.
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