Copper‐Binding Peptides Attenuate Microglia Inflammation through Suppression of NF‐kB Pathway. Issue 22 (28th September 2021)

• Record Type: Journal Article
• Authors: Caetano‐Silva, Maria Elisa; Rund, Laurie A.; Vailati‐Riboni, Mario; Pacheco, Maria Teresa Bertoldo; Johnson, Rodney W.
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 22(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-28
• Subjects: food‐derived peptides -- metal chelation -- molecular docking -- neuroinflammation -- primary microglia; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202100153
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : 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. Abstract : There is an ongoing demand for multifunctional compounds that can hinder the neurodegeneration process by different mechanisms, including anti‐inflammatory activity in microglia, the brain immune cells. Whey metal‐binding peptides decreased inflammatory markers in microglia by suppressing NF‐kB pathway. Peptides with Cu‐binding capacity might represent food‐derived peptides that can be used for neuroprotective purposes.