“The cannabinoids are a structurally diverse family of compounds with a large number of different biological targets.
Although CB1 receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism.
We have, therefore, investigated the ability of a range of cannabinoids to activate PPARα and for N-oleoylethanolamine (OEA), an endogenous cannabinoid-like compound (ECL), to evoke neuroprotection.
These data demonstrate the potential for a range of cannabinoid compounds, of diverse structures, to activate PPARα and suggest that at least some of the neuroprotective properties of these agents could be mediated by nuclear receptor activation.
In summary, the data presented here provide strong evidence that selected cannabinoids are PPARα agonists, and suggest a novel means by which the multiple effects of cannabinoids, in both the CNS and periphery, could be brought about.
In addition to its well-recognized role in lipid metabolism, PPARα activation showed obvious beneficial effects in ischaemic brain damage, which is likely to be connected with its anti-inflammatory action through the NF–κB pathway.
These discoveries not only broaden the potential use of cannabinoids as therapeutic agents, but also support PPARα as a new target for neuroprotective treatment.”