Glucose metabolism and transcriptional responses to vitamin B6 in tau-expressing fission yeast cells.

BACKGROUND: Tau pathology is increasingly recognized as a driver of metabolic dysfunction in neurodegenerative diseases, extending beyond protein aggregation to include impairments in glucose metabolism and redox homeostasis. However, how metabolic cofactors affect tau-associated metabolic stress remains incompletely understood.

METHODS AND RESULTS: In this study, we employed a fission yeast (Schizosaccharomyces pombe) model expressing human tau to investigate the effects of vitamin B6 on glucose metabolism and cellular redox balance under glucose-limited conditions in tau-expressing cells. Cells were treated with vitamin B6 and analyzed for tau expression and phosphorylation, glucose consumption, NAD⁺/NADH ratio, and the expression of selected glucose metabolism-related genes under glucose starvation conditions. Vitamin B6 treatment was associated with a reduction in tau protein expression and phosphorylation at specific residues (S262, S396, S404). In addition, vitamin B6 affected glucose metabolism-related gene expression and was accompanied by modest changes in glucose consumption and redox balance. These effects were observed in both control and tau-expressing cells, although the patterns of response differed between the two conditions. While vitamin B6 generally enhanced the expression of glucose utilization-related genes in control cells, its effects in tau-expressing cells were more variable, indicating altered metabolic regulation under tau-associated stress.

CONCLUSIONS: These findings suggest that vitamin B6 may contribute to cellular metabolic adaptation under tau-induced stress. This study demonstrates the usefulness of fission yeast as a tractable model for examining metabolic aspects of tau pathology and provides insight into how metabolic cofactors influence tau-associated cellular stress.