title: Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease.
abstract: In inflammation-associated progressive neuroinflammatory disorders, such as multiple sclerosis (MS), inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells cause demyelination and neuronal degeneration. Regulatory T cells (Treg) control the activation and infiltration of autoreactive T cells into the central nervous system (CNS). In MS and experimental autoimmune encephalomyelitis (EAE) in mice, Tregfunction is impaired. We show that a recently approved drug, Nle4-d-Phe7-α-melanocyte-stimulating hormone (NDP-MSH), induced functional Treg, resulting in amelioration of EAE progression in mice. NDP-MSH also prevented immune cell infiltration into the CNS by restoring the integrity of the blood-brain barrier. NDP-MSH exerted long-lasting neuroprotective effects in mice with EAE and prevented excitotoxic death and reestablished action potential firing in mouse and human neurons in vitro. Neuroprotection by NDP-MSH was mediated via signaling through the melanocortin-1 and orphan nuclear 4 receptors in mouse and human neurons. NDP-MSH may be of benefit in treating neuroinflammatory diseases such as relapsing-remitting MS and related disorders.
authors: Department of Dermatology, University of Münster, 48149 Münster, Germany.|Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.
authors: Nadine
authors: N
authors: Mykicki
authors: Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.|Department of Neurology, University of Münster, 48149 Münster, Germany.
authors: Alexander M
authors: AM
authors: Herrmann
authors: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors: Nicholas
authors: N
authors: Schwab
authors: Biological and Medical Research Center, University of Düsseldorf, 40225 Düsseldorf, Germany.
authors: René
authors: R
authors: Deenen
authors: Institute of Infection Immunology, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany.
authors: Tim
authors: T
authors: Sparwasser
authors: Clinic for Orthopedic and Trauma Surgery, University Clinic of Bonn, 53127 Bonn, Germany.
authors: Andreas
authors: A
authors: Limmer
authors: Department of Clinical Radiology, University of Münster, 48149 Münster, Germany.
authors: Lydia
authors: L
authors: Wachsmuth
authors: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors: Luisa
authors: L
authors: Klotz
authors: Biological and Medical Research Center, University of Düsseldorf, 40225 Düsseldorf, Germany.
authors: Karl
authors: K
authors: Köhrer
authors: Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.|Department of Clinical Radiology, University of Münster, 48149 Münster, Germany.|CRC1009 Breaking Barriers and CRC-TR 128 Multiple Sclerosis, University of Münster, 48149 Münster, Germany.
authors: Cornelius
authors: C
authors: Faber
authors: Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.|Department of Neurology, University of Münster, 48149 Münster, Germany.|CRC1009 Breaking Barriers and CRC-TR 128 Multiple Sclerosis, University of Münster, 48149 Münster, Germany.
authors: Heinz
authors: H
authors: Wiendl
authors: Department of Dermatology, University of Münster, 48149 Münster, Germany.|Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.
authors: Thomas A
authors: TA
authors: Luger
authors: Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.|Department of Neurology, University of Münster, 48149 Münster, Germany.|CRC1009 Breaking Barriers and CRC-TR 128 Multiple Sclerosis, University of Münster, 48149 Münster, Germany.
authors: Sven G
authors: SG
authors: Meuth
authors: Department of Dermatology, University of Münster, 48149 Münster, Germany. loserk@uni-muenster.de.|Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.|CRC1009 Breaking Barriers and CRC-TR 128 Multiple Sclerosis, University of Münster, 48149 Münster, Germany.
authors: Karin
authors: K
authors: Loser
mesh_terms: D000200:Action Potentials; D000818:Animals; D001812:Blood-Brain Barrier; D001854:Bone Marrow Cells / Q000378:metabolism; D049109:Cell Proliferation; D002490:Central Nervous System / Q000276:immunology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018698:Glutamic Acid / Q000737:chemistry; D006624:Hippocampus / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011485:Protein Binding; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D044102:Receptor, Melanocortin, Type 1; D018698:Glutamic Acid; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-