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Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation
Stefan Offermanns1, Markus Schwaninger2
1Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany; Medical Faculty, J.W. Goethe University, Frankfurt, Germany.
Abstract:
Neuroinflammation is a pathology common to many neurological diseases, including multiple sclerosis (MS) and stroke. However, therapeutic attempts to modulate neuroinflammation have proved difficult. Neuroinflammatory cells express HCA2, a receptor for the endogenous neuroprotective ketone body β-hydroxybutyrate (BHB) as well as for the drugs dimethyl fumarate (DMF) and nicotinic acid, which have established efficacy in the treatment of MS and experimental stroke, respectively. This review summarizes the evidence that HCA2 is involved in the therapeutic effects of DMF, nicotinic acid, and ketone bodies in reducing neuroinflammation. Furthermore, we discuss the mechanisms underlying the beneficial effects of HCA2 activation in neuroinflammatory diseases and the therapeutic potential of recently developed synthetic ligands of HCA2.
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