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Sci Transl Med. 2016 Oct 26;8(362):362ra146.

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease.

Author information

1
Department of Dermatology, University of Münster, 48149 Münster, Germany.
2
Cells in Motion-Cluster of Excellence, University of Münster, 48149 Münster, Germany.
3
Department of Neurology, University of Münster, 48149 Münster, Germany.
4
Biological and Medical Research Center, University of Düsseldorf, 40225 Düsseldorf, Germany.
5
Institute of Infection Immunology, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany.
6
Clinic for Orthopedic and Trauma Surgery, University Clinic of Bonn, 53127 Bonn, Germany.
7
Department of Clinical Radiology, University of Münster, 48149 Münster, Germany.
8
CRC1009 Breaking Barriers and CRC-TR 128 Multiple Sclerosis, University of Münster, 48149 Münster, Germany.
9
Department of Dermatology, University of Münster, 48149 Münster, Germany. loserk@uni-muenster.de.

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, Treg function 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.

PMID:
27797962
DOI:
10.1126/scitranslmed.aaf8732
[Indexed for MEDLINE]

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