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Bioorg Chem ; 145: 107242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428285

RESUMO

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.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Animais , Feminino , Gravidez , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Antioxidantes/farmacologia , Búfalos/metabolismo , Proteínas Culina/metabolismo , Caenorhabditis elegans/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Colostro/metabolismo , Estresse Oxidativo , Peptídeos/farmacologia , Peptídeos/metabolismo , Fármacos Neuroprotetores/farmacologia
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