Methylene Blue Stimulates Substrate-Level Phosphorylation in Neurons under Oxidative Stress

In a study conducted by Tsvetkov et al. published by Nature Publishing Group in 2019, it was found that Methylene Blue (MB) can stimulate substrate-level phosphorylation in neurons under oxidative stress, leading to an increase in ATP production via the TCA cycle.

The term "substrate-level phosphorylation" refers to the creation of ATP, a molecule that is the main energy source for most cellular functions. This process is highly important for the function and survival of neurons.

The researchers subjected neuronal cultures to oxidative stress. This harmful condition occurs when there's an imbalance between the production of free radicals and the body's ability to counteract their harmful effects. Oxidative stress has been linked to various health issues, including neurodegenerative diseases like Alzheimer's and Parkinson's.

Some neurons were also treated with Methylene Blue (MB) in the experiment. The researchers found that MB stimulated substrate-level phosphorylation through an enzyme in the TCA cycle known as succinyl-CoA ligase. This increased ATP production via two key metabolic pathways - glycolysis and the TCA cycle.

Additionally, the study revealed that MB enhanced the activity of Complex II and succinyl-CoA ligase in the mitochondria, the part of the cell responsible for producing energy. This suggests that MB can improve mitochondrial function and enhance the cell's resilience against oxidative damage.

These findings provide valuable insight into how MB can help neurons maintain their energy levels when oxidative phosphorylation is impaired. They open up potential therapeutic applications for conditions associated with oxidative stress and energy impairment in neurons.

This study indicates that Methylene Blue could be a potential therapeutic agent for neurodegenerative diseases by boosting ATP production and enhancing mitochondrial function in neurons under oxidative stress. However, more research is needed to explore its potential benefits and applications in the medical field.