4.8 Article

Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer's Disease-like Pathogenesis by Inhibiting Aβ Aggregation and Regulating Gut Microbiota

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 39, Pages 46406-46420

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c14818

Keywords

Alzheimer's disease; amyloid-beta; oxidative stress; neuroinflammation; gut microbiota imbalance; resveratrol-selenium-peptide nanocomposites

Funding

  1. National Natural Science Foundation of China [21701068, 21967010]

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A Res-selenium-peptide nanocomposite was developed to improve cognitive dysfunction in AD model mice by reducing Aβ aggregation, inhibiting Aβ deposition, decreasing oxidative stress and inflammation, and alleviating gut microbiota disorder.
Alzheimer's disease (AD) is a neurodegenerative disease associated with amyloid-beta (A beta ) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Resselenium-peptide nanocomposite to enable the application of Res for eliminating A beta aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and D-galactose(D-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 +/- 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood-brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 +/- 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with AP and decreasing A beta aggregation, effectively inhibiting A beta deposition in the hippocampus; (2) decreasing A beta-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating A beta-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.

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