Methylhonokiol attenuates neuroinflammation: a role for cannabinoid receptors?

The cannabinoid type-2 G protein-coupled (CB(2)) receptor is an emerging therapeutic target for pain management and immune system modulation. In a mouse model of Alzheimer’s disease (AD) the orally administered natural product 4′-O-methylhonokiol (MH) has been shown to prevent amyloidogenesis and progression of AD by inhibiting neuroinflammation. In this commentary we discuss an intriguing link between the recently found CB(2) receptor-mediated molecular mechanisms of MH and its anti-inflammatory and protective effects in AD animal models. We argue that the novel cannabimimetic MH may exert its beneficial effects via modulation of CB(2) receptors expressed in microglial cells and astrocytes. The recent findings provide further evidence for a potential role of CB(2) receptors in the pathophysiology of AD, spurring target validation and drug discovery.