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Buffalo colostrum peptide mitigates Parkinson's disease pathophysiology through Cullin-3 inhibition
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2024-02-25 , DOI: 10.1016/j.bioorg.2024.107242
Arpitha Ashok , H. Pradeep , H.S. Soundarya , H.S. Aparna

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 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

中文翻译:

水牛初乳肽通过抑制 Cullin-3 减轻帕金森病的病理生理学

初乳/牛奶是抗氧化肽的主要成分。核因子-红细胞 2 相关因子 2 (Nrf2) 是帕金森病 (PD) 的可行靶标,因为该通路被推断在 PD 中受损。 Cullin-3 是负责调节的关键 E3 连接酶之一。本研究以水牛初乳和牛奶肽为模型,筛选了水牛初乳和牛奶肽的肽文库,以抑制 Cullin-3,从而激活 Nrf2 以减轻帕金森病的分子病因学。通过对接对结构进行建模、结合位点分析并分析肽相互作用。在55个序列(≤1 kDa)中,合成了具有最高dock分数(-16.919)的肽SFVSEVPEL,并评估了其对氧化应激标志物、抗氧化酶、神经化学标志物和Nrf2/Skn-1水平的影响。先导肽减轻了与 PD 相关的氧化病理生理学和行为缺陷
更新日期:2024-02-25
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