Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
FEBS Lett. 2024 May;598(9):995-1007. doi: 10.1002/1873-3468.14835. Epub 2024 Feb 27.
Resveratrol prevents various neurodegenerative diseases in animal models despite reaching only low nanomolar concentrations in the brain after oral administration. In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found that trans-resveratrol, its conjugates (glucuronide and sulfate), and dihydro-resveratrol (intestinal microbial metabolite) bind with high affinities (K, 0.2-2 nm) to the peptide G palindromic sequence (near glycosaminoglycan-binding motif) of the 67-kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01-10 nm) of these polyphenols, especially resveratrol-glucuronide, protected neuronal cells from death induced by serum withdrawal via activation of cAMP-mediated signaling pathways. This protection was prevented by a 67LR-blocking antibody, suggesting a role for this cell-surface receptor in neuroprotection by resveratrol metabolites.
白藜芦醇在经口服后，尽管在大脑中的浓度仅达到低纳摩尔水平，但仍能预防各种神经退行性疾病。在这项研究中，基于内源性色氨酸荧光的猝灭和分子对接，我们发现反式白藜芦醇、其轭合物（葡萄糖醛酸苷和硫酸盐）和二氢白藜芦醇（肠道微生物代谢物）与 67 kDa 层粘连蛋白受体（67LR）的肽 G 回文序列（靠近糖胺聚糖结合基序）具有高亲和力（K，0.2-2nm）。用这些多酚（特别是白藜芦醇葡萄糖醛酸苷）的低浓度（0.01-10nm）预处理，可以通过激活 cAMP 介导的信号通路，保护神经元细胞免受血清剥夺诱导的死亡。这种保护作用被 67LR 阻断抗体所阻止，这表明这种细胞表面受体在白藜芦醇代谢物的神经保护中发挥作用。
