title: Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation.
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.
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany; Medical Faculty, J.W. Goethe University, Frankfurt, Germany. Electronic address: Stefan.offermanns@mpi-bn.mpg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany; DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany. Electronic address: markus.schwaninger@pharma.uni-luebeck.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy; D055423:Diet, Ketogenic; D000069462:Dimethyl Fumarate / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D009103:Multiple Sclerosis / Q000178:diet therapy / Q000188:drug therapy*; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000178:diet therapy / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology; D020521:Stroke / Q000178:diet therapy / Q000188:drug therapy
chemical_list: D018696:Neuroprotective Agents; D009525:Niacin; C579271:ADCY10 protein, human; D000262:Adenylyl Cyclases; D000069462:Dimethyl Fumarate; D020155:3-Hydroxybutyric Acid
keywords: G protein-coupled receptor; cerebral ischemia; experimental autoimmune encephalomyelitis; hydroxy carboxylic acid receptor; ketogenic diet; multiple sclerosis