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

2.50
Hdl Handle:
http://hdl.handle.net/10033/620911
Title:
Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease.
Authors:
Mykicki, Nadine; Herrmann, Alexander M; Schwab, Nicholas; Deenen, René; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Limmer, Andreas; Wachsmuth, Lydia; Klotz, Luisa; Köhrer, Karl; Faber, Cornelius; Wiendl, Heinz; Luger, Thomas A; Meuth, Sven G; Loser, Karin
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.
Affiliation:
TWINCORE; Zentrum für experimentelle und klinische Infectionsforsching GmbH, Feodor-Lynen Str. 17, 30625 Hannover, Germany.
Citation:
Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. 2016, 8 (362):362ra146 Sci Transl Med
Journal:
Science translational medicine
Issue Date:
26-Oct-2016
URI:
http://hdl.handle.net/10033/620911
DOI:
10.1126/scitranslmed.aaf8732
PubMed ID:
27797962
Type:
Article
Language:
en
ISSN:
1946-6242
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorMykicki, Nadineen
dc.contributor.authorHerrmann, Alexander Men
dc.contributor.authorSchwab, Nicholasen
dc.contributor.authorDeenen, Renéen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorLimmer, Andreasen
dc.contributor.authorWachsmuth, Lydiaen
dc.contributor.authorKlotz, Luisaen
dc.contributor.authorKöhrer, Karlen
dc.contributor.authorFaber, Corneliusen
dc.contributor.authorWiendl, Heinzen
dc.contributor.authorLuger, Thomas Aen
dc.contributor.authorMeuth, Sven Gen
dc.contributor.authorLoser, Karinen
dc.date.accessioned2017-05-08T12:21:56Z-
dc.date.available2017-05-08T12:21:56Z-
dc.date.issued2016-10-26-
dc.identifier.citationMelanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. 2016, 8 (362):362ra146 Sci Transl Meden
dc.identifier.issn1946-6242-
dc.identifier.pmid27797962-
dc.identifier.doi10.1126/scitranslmed.aaf8732-
dc.identifier.urihttp://hdl.handle.net/10033/620911-
dc.description.abstractIn 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleMelanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease.en
dc.typeArticleen
dc.contributor.departmentTWINCORE; Zentrum für experimentelle und klinische Infectionsforsching GmbH, Feodor-Lynen Str. 17, 30625 Hannover, Germany.en
dc.identifier.journalScience translational medicineen

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