SVα-MSH, a novel α-melanocyte stimulating hormone analog, ameliorates autoimmune encephalomyelitis through inhibiting autoreactive CD4+ T cells activation

Fang, Jie; Han, Deping; Hong, Jinsheng; Zhang, Hengshan; Ying, Ying; Tian, Yeping; Zhang, Lurong; Lin, Jianhua

doi:10.1016/j.jneuroim.2014.01.010

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…1G and Fig. 8B), the different efficacy of Ac-SV-MSH and NDP-MSH might be explained by the specificity of NDP-MSH for Mc1r, whereas Ac-SV-MSH binds to Mc1r and Mc5r with similar affinity (18,23,24).…”

Section: Discussionmentioning

confidence: 98%

“…Hence, the majority of Mc1r-mediated effects of a-MSH are based on the activation of cyclic adenosine monophosphate (cAMP)-dependent signaling pathways. These include the activation of protein kinase A, the phosphorylation of cAMP response element-binding protein (CREB), the reduction of nuclear factor of activated T cells (NFAT) activity, or the suppression of nuclear factor kB (NF-kB) translocation through the protection of inhibitor of nuclear factor kB a (IkBa) from phosphorylation (18,19). Under physiologic conditions, cells of the CNS are a source of a-MSH, and in vitro studies suggest a possible neuroprotective role because melanocortin inhibited NF-kB activation in tumor necrosis factor a-activated rat Schwann cells or lipopolysaccharide-activated human glioma cells (20,21).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…The neuroprotective functions of α-MSH can also reduce the severity of autoimmune encephalomyelitis (EAE) in rodent models. 85 , 114 This contrasts with GCs, which have been found to increase apoptosis of retinal nerve ganglion cells in EAE models. 115 EAE is an inflammatory demyelinating disease of the central nervous system which, importantly, is a model system for multiple sclerosis (MS).…”

Section: Melanocortins As Alternatives To Glucocorticoidsmentioning

confidence: 94%

The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids

Clemson

Yost

Taylor

2016

Ocular Immunology and Inflammation

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Melanocortins are a highly conserved family of peptides and receptors that includes multiple proopiomelanocortin-derived peptides and five defined melanocortin receptors. The melanocortins have an important role in maintaining immune homeostasis and in suppressing inflammation. Within the healthy eye, the melanocortins have a central role in preventing inflammation and maintaining immune privilege. A central mediator of the anti-inflammatory activity is the non-steroidogenic melanocortin peptide alpha-melanocyte stimulating hormone. In this review we summarize the major findings of melanocortin regulation of ocular immunobiology with particular interest in the ability of melanocortin to induce immune tolerance and cytoprotection. The melanocortins have therapeutic potential because their mechanisms of action in regulating immunity are distinctly different from the actions of steroids.

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“…α-MSH, which cannot signal through MC2R expressed in the adrenals, inhibits the development of EAE [ 81 , 82 ] and EAN [ 83 ], a peripheral neuropathy, that serves as a model for some variants of Guillain-Barre Syndrome (GBS). An α-MSH analog, SValpha-MSH also inhibits EAE, acting to inhibit CD4+ T cells [ 84 ]. Since α-MSH cannot increase endogenous corticosteroids and yet inhibits development of EAN, this supports the idea that inhibition of EAN is due to the direct effects of α-MSH on immune cells and/or Schwann cells, the myelin forming cells of the PNS.…”

Section: Effects On Endogenous Cells Of the Cns With Potential Promentioning

confidence: 99%

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Lisak

Benjamins

2017

Brain Sciences

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The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cells (lymphocytes and monocytes) and by signaling through CNS cells in regions lacking a mature blood brain barrier are clear. However, additional studies are needed to develop highly effective MCR targeted therapies that directly affect endogenous cells of the CNS, particularly OL, their progenitors and neurons.

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SVα-MSH, a novel α-melanocyte stimulating hormone analog, ameliorates autoimmune encephalomyelitis through inhibiting autoreactive CD4+ T cells activation

Cited by 7 publications

References 33 publications

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

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

The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

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