PPARα is part of the nuclear receptor family and is therefore one of the non-GPCR cannabinoid receptors. PPAR-alpha is a transcription factor and a major regulator of lipid metabolism in the liver. Low energy typically stimulates PPARα, but PPARα has also been implicated in neuroprotection.

Chemical Name: 
Peroxisome proliferator-activated receptor alpha
IUPHAR entry: 
Wikipedia entry: 
Distribution: 

Expression of PPAR-alpha is highest in tissues that oxidize fatty acids at a rapid rate and in liver, intestine, heart and kidney.

Literature Discussion: 

Alzheimer´s

Endogenous PEA levels rise with astrogliosis. PEA, in turn, blocks pro-inflammatory cytokines through PPARα (Scuderi et al., 2011). This suggests that the PEA-PPARα interaction functions to curtail neuroinflammation and inhibit the progression of Alzheimer’s.

Autism

In a rat model of Autism (Valproic Acid model), GPR55, PPARα and PPARγ were reduced in several brain regions involved in higher cognitive functions (frontal cortex and hippocampus) (Kerr et al., 2013)

Bulimia

OEA reduced food intake and weight gain in rodents via PPARα and TRPV1 (Overton et al., 2006).

Cystitis

A rat study found that endocannabinoid PEA and CB1 were upregulated, PPARα was downregulated and CB2 was unchanged upon induction of Cystitis (Pessina et al., 2014). PEA attenuated pain and bladder voiding. This effect was blocked by CB1 and PPARα antagonists.

Eczema

In an experimental mouse model of Eczema endocannabinoids AEA and PEA were increased and TRPV1 and PPARα were upregulated (Petrosino et al., 2010). PEA enhances AEA activity at CB1CB2 and TRPV1 receptors and protects against keratinocyte inflammation in a TRPV1-, but not CB1CB2 or PPARα-dependent way.

References:

Kerr, D.M., Downey, L., Conboy, M., Finn, D.P., and Roche, M. (2013). Alterations in the endocannabinoid system in the rat valproic acid model of Autism. Behav. Brain Res. 249, 124–132.

Overton, H.A., Babbs, A.J., Doel, S.M., Fyfe, M.C.T., Gardner, L.S., Griffin, G., Jackson, H.C., Procter, M.J., Rasamison, C.M., Tang-Christensen, M., et al. (2006). Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 3, 167–175.

Pessina, F., Capasso, R., Borrelli, F., Aveta, T., Buono, L., Valacchi, G., Fiorenzani, P., Di Marzo, V., Orlando, P., and Izzo, A.A. (2014). Protective Effect of Palmitoylethanolamide in a Rat Model of Cystitis. J. Urol.

Petrosino, S., Cristino, L., Karsak, M., Gaffal, E., Ueda, N., Tüting, T., Bisogno, T., De Filippis, D., D’Amico, A., Saturnino, C., et al. (2010). Protective role of palmitoylethanolamide in contact allergic dermatitis. Allergy 65, 698–711.

Scuderi, C., Esposito, G., Blasio, A., Valenza, M., Arietti, P., Steardo, L., Carnuccio, R., De Filippis, D., Petrosino, S., Iuvone, T., et al. (2011). Palmitoylethanolamide counteracts reactive astrogliosis induced by β-amyloid peptide. J. Cell. Mol. Med. 15, 2664–2674.