α-MSH Peptides Inhibit Production of Nitric Oxide and Tumor Necrosis Factor-α by Microglial Cells Activated with β-Amyloid and Interferon γ
Abstract
Alpha-melanocyte stimulating hormone (alpha-MSH) is an ancient tridecapeptide with potent inhibitory activity in all major forms of inflammation. The anti-inflammatory message sequence of alpha-MSH resides in the COOH-terminal tripeptide alpha-MSH[11-13]. We tested the influence of alpha-MSH[1-13] and of alpha-MSH[11-13] in a cultured murine microglia cell line known to produce nitric oxide (NO(-)(2)) and tumor necrosis factor (TNFalpha) when stimulated with beta-amyloid protein (Abeta). Melanocortin peptides significantly inhibited release of both NO(-)(2) and TNFalpha into cell-free supernatants from microglia stimulated with Abeta[1-42] or Abeta[25-35] peptides and interferon gamma (IFNgamma). Northern blot analysis demonstrated that alpha-MSH[1-13] and alpha-MSH[11-13] inhibited accumulation of inducible nitric oxide synthase (iNOS) and TNFalpha mRNA was triggered by Abeta stimulation. Abeta/microglial interaction is believed to promote the progression of inflammatory and neurodegenerative changes in senile plaques in Alzheimer's disease. Our data indicate that alpha-MSH peptides might be used to modulate the local response of the brain to Abeta deposition in this neurodegenerative disease.
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In Alzheimer's disease, reactive microglia and astrocytes are associated with amyloid plaques and respond to Aβ with expression of pro-inflammatory cytokines.
“In AD, reactive microglia and astrocytes are associated with the amyloid plaques and respond to Aβ with the expression of pro-inflammatory cytokines [12,13,14].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [14]
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- Authors
- Galimberti, D., Baron, P., Meda, L., Prat, E., Scarpini, E., Delgado, R., Catania, A., Lipton, J. M., & Scarlato, G.
- Affiliations
- University of Milan (IT)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Baron, Pierluigi
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 263
- Issue
- 1
- Pages
- 251-256
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2435170652
- Cited by
- 83
- References
- 34
- Citations by year
- 2024: 2 · 2023: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 2
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- alpha-melanocyte-stimulating hormone, microglia, nitric oxide, TNF-α, amyloid-beta, interferon-gamma, inducible nitric oxide synthase, anti-inflammatory peptides, Alzheimer's disease, neuroinflammation, amyloid plaques
- MeSH terms
- alpha-MSH, Animals, Cell Line, Interferon-gamma, Melanocyte-Stimulating Hormones, Nitric Oxide, Peptide Fragments, Recombinant Proteins, RNA, Messenger, Tumor Necrosis Factor-alpha, Amyloid beta-Peptides, Microglia, Inflammation Mediators, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II
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