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 (PPARα), which belongs
to the family of nuclear receptor ligand-activated transcription factors that includes PPARβ/δ and
PPARγ. A growing body of evidence supports the notion that PPARα 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 PPARα. More recently,
studies have reported the permissive role of PPARα 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 PPARα 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 PPARα 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 PPARα 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 PPARα in sleep abnormalities.