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Cited by 27Multiple Sclerosis Research StudiesNeuropeptides and Animal PhysiologyNeuroinflammation and Neurodegeneration Mechanisms

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

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Lisak, Robert, Benjamins, Joyce·2017·Brain Sciences
DOI 10.3390/brainsci7080104PMC PMC5575624
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Abstract

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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  • Previously, direct receptor-mediated anti-inflammatory effects of ACTH and succinate on immune cells associated with blockages of pro-inflammatory polarization have been shown.

    “Previously, the direct receptor-mediated anti-inflammatory effects of ACTH and succinate on immune cells associated with blockages of pro-inflammatory polarization have been shown [51,52,89].”

    From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [52]

    Section 5.2 (page not provided) says melanocortin-receptor signaling in immune cells inhibits inflammation and is associated with a shift away from proinflammatory lymphocyte effects. It also reports nonsteroidogenic anti-inflammatory effects of ACTH, but cautions that direct effects are difficult to demonstrate when ACTH raises corticosteroids. The paper does not address succinate, so it does not support that part of the attributed claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The drugs' abilities to exert neurotrophic effects may be mediated by activation of specific receptors: SUCNR1 for Mexidol and MCRs for Semax.

    “The drugs’ abilities to exert neurotrophic effects may be mediated by the activation of specific receptors: SUCNR1 for Mexidol and receptors of the melanocortin family MCRs for Semax [51,52,59,60].”

    From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [52]

    Section 7 reports that melanocortins have trophic effects on neurons, while Sections 6.2 and 7 describe protective effects associated with melanocortin receptors. The paper does not identify Semax or establish that its neurotrophic effects are mediated by MCR activation. The sentence has multiple citations; its separate Mexidol–SUCNR1 claim is not addressed by this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Treatment with Mexidol and Semax, especially Mexidol, prolonged the period of PGC-1α activation, which may be related to receptor-mediated (by SUCNR1 and MCRs) initiation of calcium signaling cascades in neurons.

    “The treatment with Mexidol and Semax, especially Mexidol, prolonged the period of PGC-1α activation, which may be related to the receptor-mediated (by SUCNR1 and MCRs) initiation of calcium signaling cascades in neurons [51,52,59,60].”

    From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [52]

    Section 4 (page unavailable) reports that melanocortin-receptor signaling can increase intracellular calcium, and Section 6.2 discusses MC4R effects in neurons. The paper does not report that Mexidol or Semax prolongs PGC-1α activation or link either treatment to SUCNR1- or MCR-mediated calcium signaling. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In models of brain ischaemia and inflammation, α-MSH exhibits strong anti-inflammatory, neurogenic and neuroprotective effects.

    “Additionally, in models of brain ischaemia and inflammation, α-MSH exhibits strong anti-inflammatory, neurogenic and neuroprotective effects [65,66,67].”

    From Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats (2020) · cites this paper as [66]

    Sections 5.2 and 7 report anti-inflammatory effects of α-MSH and neuroprotection by melanocortins in CNS injury and neuroinflammatory models. Section 6.2 mentions neurogenesis in an Alzheimer’s model following MC4R activation, but the copy does not establish the claimed combination of effects for α-MSH in models of brain ischaemia and inflammation. Page numbers were not available in the indexed passages. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Lisak, R., & Benjamins, J.
Affiliations
Wayne State University (US)
Corresponding author
Lisak, Robert
ORCID
Venue
Brain Sciences
Publisher
MDPI AG
Published
2017-08-14
Volume
7
Issue
8
Pages
104
ISSN
2076-3425 (ISSN-L)
DOI
10.3390/brainsci7080104
PMC
PMC5575624
OpenAlex
W2747864218
Cited by
27
References
5
Citations by year
2025: 5 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 2 · 2018: 3 · 2017: 1
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Sanofi
  • Genentech
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
melanocortin peptides, melanocortin receptors, multiple sclerosis, oligodendrocytes, neuroprotection, CNS repair, peripheral immune system, hypothalamic-pituitary-adrenal axis, myelin, neuroinflammation, targeted therapy

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