In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 8, No. 362 ( 2016-10-26)
Abstract:
In inflammation-associated progressive neuroinflammatory disorders, such as multiple sclerosis (MS), inflammatory infiltrates containing T helper 1 (T H 1) and T H 17 cells cause demyelination and neuronal degeneration. Regulatory T cells (T reg ) control the activation and infiltration of autoreactive T cells into the central nervous system (CNS). In MS and experimental autoimmune encephalomyelitis (EAE) in mice, T reg function is impaired. We show that a recently approved drug, Nle 4 - d -Phe 7 –α-melanocyte–stimulating hormone (NDP-MSH), induced functional T reg , 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.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.aaf8732
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2016
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