Black soybean peptide mediates the AMPK/SIRT1/NF-κB signaling pathway to alleviate Alzheimer's-related neuroinflammation in lead-exposed HT22 cells

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by hyperphosphorylation of tau, neuroinflammation, and amyloid-beta (Aβ) plaques. Lead (Pb) exposure has been linked to an increased risk of AD and neuroinflammation. The purpose of this study is to determine if black soybean peptide (BSP1) may reduce neuroinflammation caused by Pb and associated AD-like pathology. Pb exposure was given to mouse hippocampus HT22 cells in the presence or absence of BSP1, positive control resveratrol (Rsv), or the SIRT1 inhibitor EX-527. Our findings suggest that BSP1 downregulates the expression of beta-secretase (BACE1) and amyloid precursor protein (APP), inhibits tau phosphorylation, and reduces Aβ1-42 deposition. In addition, BSP1 effectively alleviated Pb-induced neuroinflammation by reducing the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines (IL-1β, TNF-α, NLRP3, and IL-18). BSP1 provides neuroprotective effect via phosphorylating LKB1 and AMPK, inhibiting mTOR signaling, and activating the AMPK/SIRT1 pathway. These results suggest that BSP1 may be therapeutically beneficial for preventing or treating AD by reducing Pb-induced neuroinflammation.

Keywords: AMPK/SIRT1/NF-κB pathway; Alzheimer's disease; Black soybean peptide; Lead (Pb); Neuroinflammation.