Recombinant protein LPxT-GYLEQ attenuates cognitive impairment by ameliorating oxidative stress in D-galactose-induced aging mice model

Food-derived antioxidant peptides have been shown to have beneficial effects in scavenging excess free radicals. In this study, a novel multifunctional LPxTG-motif protein LPxT-GYLEQ was synthesized, and its molecular mechanism of alleviating cognitive impairment in a D-galactose (D-gal)-induced aging mice model was also investigated. The results confirmed the antioxidant effects of the LPxT-GYLEQ protein, which could scavenge excessive reactive oxygen species (ROS) in aging mice by regulating the c-Jun N-terminal kinase (JNK)/Nuclear factor erythroid 2-related factor 2 (Nrf2)/p38/Nuclear factor-k-gene binding (NF-κB) signal pathway, reduced the accumulation of β-amyloid protein (Aβ), restored the cognitive ability of mice, improved learning and memory behavior, effectively reduced the expression of inflammatory-related factors, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and increased the expression of anti-inflammatory factor interleukin-10 (IL-10). These may be related to the fact that the protein regulates the abundance of beneficial bacteria such as intestinal Akkermansia Muciniphila (Akk). All results suggest that the synthetic LPxT-GYLEQ protein may improve cognitive impairment and be a promising candidate for an anti-aging agent.