Begüm Öğünç, Nur Ramoğlu, Irmak Sakin

Acıbadem University School of Medicine, Istanbul, Turkey

Keywords: Alzheimer’s disease, inflammatory bowel disease, methylene blue


High-efficiency oxidative phosphorylation plays a key role in the progression of many diseases. There is growing evidence of methylene blue’s protective and reversing actions against neurodegenerative and inflammatory bowel diseases through different mechanisms. In Alzheimer’s disease (AD), oligomeric amyloid beta accumulates in the mitochondria and contributes to mitochondrial dysfunction, which occurs before significant plaque deposition. Methylene blue provides an alternative mitochondrial electron transfer pathway, switching from high-efficiency oxidative phosphorylation to the low-efficiency aerobic glycolysis pathway by receiving electrons from NADH in the presence of complex I and transferring them to cytochrome C. The second mechanism is the inhibition of active caspases, especially Caspase-6, a cysteinyl protease causing inflammation and cell death, which has been associated with age-dependent cognitive decline and the pathology of sporadic and familial AD. The third mechanism is the reversal of tau aggregation by oxidizing cysteine residues in tau and forming a more stable monomer, thus blocking tau-tau bindings as well as clearing tau pathology through increased autophagy. In regards to inflammatory bowel disease, reducing oxidative stress and attenuating inflammatory pathways inhibits epithelial destruction in acetic acid-induced colitis. Methylene blue has an anti-colitis effect, mainly relying on its mitochondrial efficacy-restoring, antioxidative, anti-inflammatory, and anti-apoptotic properties. In summary, methylene blue is a promising agent for both AD and inflammatory bowel disease due to its beneficial effects as well as its low cost and high accessibility.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

The authors received no financial support for the research and/or authorship of this article.