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J Neuroinflammation. 2012 Jun 20;9:135. doi: 10.1186/1742-2094-9-135.

Methylhonokiol attenuates neuroinflammation: a role for cannabinoid receptors?

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  • 1Institute of Biochemistry and Molecular Medicine, National Centre of Competence in Research NCCR TransCure, University of Bern, Bühlstrasse 28, Bern CH-3012, Switzerland.


The cannabinoid type-2 G protein-coupled (CB₂) 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 CB₂ 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 CB₂ receptors expressed in microglial cells and astrocytes. The recent findings provide further evidence for a potential role of CB₂ receptors in the pathophysiology of AD, spurring target validation and drug discovery.

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