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Copper-Binding Peptides Attenuate Microglia Inflammation through Suppression of NF-kB Pathway
Maria Elisa Caetano-Silva1,2, Laurie A Rund2, Mario Vailati-Riboni2
1Center of Food Science and Quality (CCQA), Institute of Food Technology (Ital), Campinas, SP, 13070-178, Brazil.
Scope:
Activation of microglia, the resident immune cells of the central nervous system, has been related to the etiology and progression of neurodegenerative diseases; thus, finding novel approaches to suppress the neuroinflammatory process is of utmost relevance.
Methods And Results:
The anti-inflammatory activity of whey Cu-, Fe-, and Zn-binding peptides and their possible underlying mechanism of action were evaluated in microglia. Whey metal-binding peptides decreased nitric oxide production and tumor necrosis factor α (TNF-α) at mRNA and protein levels by stimulated BV-2 microglia in comparison to the control with no peptide treatment. The hydrophobicity, specific sequences, and possible synergistic effects seem to play a role. Cu-binding peptides (Cu-bp) presented anti-inflammatory activity both in BV-2 and primary microglia cultures. These peptides exert their action by suppressing nuclear factor kappa B (NF-kB) pathway since nuclear translocation of NF-kB p65 is decreased by roughly 30% upon Cu-bp treatment. Specific sequences identified in Cu-bp showed high affinity to bind NF-kB p65 by molecular docking (up to -8.8 kcal mol-1 ), corroborating the immunofluorescence studies.
Conclusion:
Cu-bp represent food-derived peptides that may be useful for neuroprotective purposes. Chelation of copper excess in the CNS and the bioavailability of such peptides, as well as their behavior in in vivo models, deserve further research for future applications.
Insights
Whey peptides, particularly copper-binding peptides (Cu-bp), reduce neuroinflammation by inhibiting key inflammatory pathways in microglia. These food-derived peptides show promise for neuroprotection and warrant further investigation in vivo.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Microglia activation is implicated in neurodegenerative diseases.
- Suppressing neuroinflammation is crucial for therapeutic interventions.
Purpose of the Study:
- To evaluate the anti-inflammatory effects of whey metal-binding peptides in microglia.
- To elucidate the mechanism of action of these peptides.
Main Methods:
- Assessed anti-inflammatory activity of whey Cu-, Fe-, and Zn-binding peptides in BV-2 and primary microglia.
- Measured nitric oxide and TNF-α production at mRNA and protein levels.
- Investigated the nuclear factor kappa B (NF-kB) pathway suppression using molecular docking and immunofluorescence.
Main Results:
- Whey metal-binding peptides reduced nitric oxide and TNF-α levels.
- Copper-binding peptides (Cu-bp) demonstrated significant anti-inflammatory effects.
- Cu-bp suppressed NF-kB pathway activation by decreasing p65 nuclear translocation by approximately 30%.
Conclusions:
- Cu-bp exhibit anti-inflammatory properties and may be beneficial for neuroprotection.
- Further research on Cu-bp bioavailability and in vivo efficacy is needed for therapeutic applications.
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