中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (3): 819-820.doi: 10.4103/NRR.NRR-D-24-00160

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

白藜芦醇葡糖苷酸和槲皮素葡糖苷酸通过与层粘连蛋白受体中的多酚和糖胺聚糖结合位点结合的神经保护作用

  


  • 出版日期:2025-03-15 发布日期:2024-06-26

Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol- and glycosaminoglycan-binding sites in the laminin receptor

Rayudu Gopalakrishna*, Jennifer Aguilar, Emily Lee, William J. Mack   

  1. Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA (Gopalakrishna R, Aguilar J, Lee E)
    Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA (Mack WJ)
  • Online:2025-03-15 Published:2024-06-26
  • Contact: Rayudu Gopalakrishna, PhD, rgopalak@usc.edu.
  • Supported by:
    This work was supported by NIH grants, NINDS R21 NS116720 and NINDS/NIA RF1 NS130681 (to RG and WJM).

摘要: https://orcid.org/0000-0002-0398-3166 (Rayudu Gopalakrishna)

Abstract: The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models; however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated forms, and not as the aglycone parent form (Pasinetti et al., 2015). Recently, we found that these polyphenol aglycones and glucuronide metabolites bind with high affinity to two sites present within the peptide G region of 67-kDa laminin receptor (67LR): the “A” site, which is supported by the more hydrophobic palindromic sequence in peptide G and the “B” site, which is supported by the less hydrophobic N-terminal half of peptide G (Gopalakrishna et al., 2023, 2024). The glycosaminoglycan (GAG)-binding motif present in peptide G recognizes both the glucuronic acid moiety of glucuronide metabolites of polyphenols and the gallic acid moiety of (–)-epigallocatechin-3-gallate (EGCG) in A and B sites (Figure 1). These glucuronidated metabolites protect neuronal cells from cell death more effectively than the aglycone parent polyphenols (Gopalakrishna et al., 2023). Some dietary polyphenols may have common targets and mechanisms of neuroprotective action and may produce additive/synergistic interactions. This information may help optimize the prevention of neurodegenerative diseases with a rational combination of low doses of polyphenols for safer dietary supplementation in humans.