The Role of Nuclear Receptor PPARa in the Sleep-wake Cycle Modulation. A Tentative Approach for Treatment of Sleep Disorders

Background: There is a general consensus that sleep-wake cycle is controlled by neuroanatomical, neurochemical and molecular systems as well as by homeostatic and circadian complex networks. The research has shown that a molecular element that could be displaying a relevant role in the modulation of sleep is the peroxisome proliferator-activated receptor alpha (PPAR alpha), which belongs to the family of nuclear receptor ligand-activated transcription factors that includes PPAR beta/delta and PPAR gamma. A growing body of evidence supports the notion that PPAR alpha is activated by natural ligands such as the anorexic lipid mediator oleoylethanolamide (OEA) or synthetic compounds including Wy14643 whereas antagonists like MK-886 block the neurobiological outcomes of PPAR alpha. More recently, studies have reported the permissive role of PPAR alpha by modulating diverse neurobiological functions such as inflammation, metabolic disorders, learning, degenerative diseases and sleep. Remarkably, this nuclear receptor has been described in sleep-related brain regions leading to the hypothesis that PPAR alpha might be involved in sleep modulation inasmuch as activation of this protein promotes a robust enhancement of wakefulness while reduces sleep. Objective: In this mini review, the emerging evidence of the putative role of PPAR alpha in sleep control is highlighted. Even though the data are derived from new areas of research, there are many reasons to believe that understanding and appreciation of PPAR alpha functions may provide knowledge of possible mechanisms of action activated by this nuclear receptor in sleep modulation. Conclusion: Novel insights of therapeutic intervention for sleep disorders might be visualized targeting the function of PPAR alpha in sleep abnormalities.