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Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease.
Mykicki, Nadine Herrmann, Alexander M Schwab, Nicholas Deenen, René Limmer, Andreas Wachsmuth, Lydia Klotz, Luisa Köhrer, Karl Faber, Cornelius
Mykicki, Nadine
Herrmann, Alexander M
Schwab, Nicholas
Deenen, René
Limmer, Andreas
Wachsmuth, Lydia
Klotz, Luisa
Köhrer, Karl
Faber, Cornelius
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2016-10-26
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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, Nle(4)-d-Phe(7)-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.
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Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. 2016, 8 (362):362ra146 Sci Transl Med
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en
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1946-6242