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Bioorg Chem ; 145: 107242, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38428285

ABSTRACT

Colostrum/Milk is a chief repertoire of antioxidant peptides. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a viable target for Parkinson's Disease (PD), as this pathway deduced to be impaired in PD. Cullin-3 is one of the crucial E3 ligase responsible for its regulation. The present study screened peptide libraries of buffalo colostrum & milk peptides for Cullin-3 inhibition, thus ensuing activation of Nrf2 to alleviate the molecular etiopathology in PD using the C. elegans as a model. The structure was modelled, binding sites analyzed and peptide-interactions analyzed by docking. Among the 55 sequences (≤1 kDa), the peptide SFVSEVPEL having the highest dock score (-16.919) was synthesized and evaluated for its effects on oxidative stress markers, antioxidant enzymes, neurochemical marker and Nrf2/Skn-1 levels. The lead peptide alleviated the oxidative pathophysiology and behavioural deficits associated with PD in C. elegans.


Subject(s)
Neuroprotective Agents , Parkinson Disease , Animals , Female , Pregnancy , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Antioxidants/pharmacology , Buffaloes/metabolism , Cullin Proteins/metabolism , Caenorhabditis elegans/metabolism , NF-E2-Related Factor 2/metabolism , Colostrum/metabolism , Oxidative Stress , Peptides/pharmacology , Peptides/metabolism , Neuroprotective Agents/pharmacology
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