Mitigation of Z1 on Methylglyoxal-Induced Glycotoxicity in Neuron-2A Cells by Enhancing Detoxification Pathways.

Methylglyoxal (MGO), a reactive byproduct of microbial metabolism, contributes to neurodegeneration and may be further exacerbated by gut dysbiosis. Probiotic strategies that restore microbial balance and barrier integrity thus represent a promising therapeutic approach. In this study, we explored the neuroprotective potential of the probiotic strain Z1 ( Z1) in MGO-challenged mouse neuronal cells (N2a). Z1 treatment effectively reduced apoptosis and reactive oxygen species (ROS) production, indicating its substantial neuroprotective activity. Mechanistically, Z1 treatment downregulated apoptotic signaling pathways involving mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, Z1 enhanced cellular detoxification through activation of the glyoxalase system and bolstered antioxidant defenses induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Metabolite analysis identified bioactive compounds within Z1, notably tryptophan, which exhibited a high affinity for MGO and modulated the expression of apoptosis-related proteins. Our findings indicate that Z1 and its microbial bioactive metabolites, including tryptophan, may serve as potential nutraceutical candidates for neuroprotection against glycotoxins such as MGO.