| First Author | Mykicki N | Year | 2016 |
| Journal | Sci Transl Med | Volume | 8 |
| Issue | 362 | Pages | 362ra146 |
| PubMed ID | 27797962 | Mgi Jnum | J:252849 |
| Mgi Id | MGI:5924452 | Doi | 10.1126/scitranslmed.aaf8732 |
| Citation | Mykicki N, et al. (2016) Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. Sci Transl Med 8(362):362ra146 |
| abstractText | 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-alpha-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. |
