Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions

Abstract

Abstract Oxidative stress is damaging to cells and contributes to aging and neurodegenerative disease. This state is mediated by production of imbalanced molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The glyoxalase pathway is an antioxidant defense system utilized to detoxify methylglyoxal and neutralize free radicals. Pathway dysfunction leads to overproduction and accumulation of toxic, prooxidant compounds. We hypothesize flavonoid treatment as a means to enhance the glyoxalase pathway’s ability to detoxify in neurons. This study found that flavonoid treatment in methylglyoxal treated cerebellar neurons increased the functioning of glyoxalase pathway by enhancing expression of glyoxalase-1 and glyoxalase-2 proteins, decreased cell death and increased cellular viability. Flavonoids also significantly contributed in the retention of synaptic functions (VGLUT1 and GAD65) in cerebellar neurons. In addition, flavonoids were found to be involved in pAkt - NF-κB signaling pathway through a reduction in phosphorylation of Akt. The data here show flavonoid compounds have the potential to protect the brain from aging and neurodegenerative disease.