Vitamin B6 Modifies Tau-Induced Cellular Stress- and Proteostasis-Related Responses

Abnormal tau expression is associated with disruption of cellular homeostasis and activation of stress-response pathways. However, the effects of vitamin B6 on cellular stress responses associated with tau expression remain unclear. In this study, the influence of vitamin B6 on oxidative stress responses, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling, autophagy-related gene expression, and apoptosis-related responses was investigated using a human tau-expressing Schizosaccharomyces pombe model. Cells expressing human tau were treated with pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, and changes in oxidative stress responses, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling, autophagy-related gene expression, apoptosis-related responses, and protein carbonyl content were evaluated. Tau expression was associated with increased expression of oxidative stress-, ER stress-, and autophagy-related genes. Vitamin B6 altered several of these responses, including the expression of ER stress- and oxidative stress-related genes. Although intracellular ROS levels increased following vitamin B6 treatment, protein carbonyl levels remained largely unchanged. In contrast, apoptosis-related responses showed only limited changes. These findings show that vitamin B6 is associated with changes in selected stress- and proteostasis-related responses in tau-expressing cells. The observed effects were not uniform across all pathways, indicating a complex relationship between vitamin B6, tau expression, and cellular stress responses. This study provides further insight into cellular responses associated with tau expression and supports further investigation of vitamin B6-mediated effects in more complex experimental models.