Molecular hydrogen may activate the transcription factor Nrf2 to alleviate oxidative stress through the hydrogen-targeted porphyrin

Oxidative stress is one of the major causes most age-dependent neurodegenerative disorders. Neurons accumulate oxidative damage over time due to post-mitotic cells. Thus, modulation essential overcome these Molecular hydrogen (H2) has great potential for treating various diseases and improving quality life by exerting multiple functions including anti-oxidation, anti-inflammation, energy metabolism promotion. Among functions, H2 activates a transcription factor, nuclear factor erythroid 2-related 2 (Nrf2) enhance transcribe broad range anti-stress enzymes, antioxidant enzymes. There was an elusive contradiction between Nrf2 because activated in response stress, whereas reducing potential. The target molecule recently been identified as oxidized form Fe-porphyrin conjugated with -OH group (PrP-Fe(III)-OH). As initial step, hydroxyl radical (•OH) oxidizes heme (PrP-Fe(II)) PrP-Fe(III)-OH. Then, reacts PrP-Fe(III)-OH produce PrP-Fe(III)-H H2O. In turn, Fe(III) H act electrophile oxidize Kelch-like ECH-associated protein 1 (Keap1), resulting activating Nrf2. when original highly damaging electrophilicity •OH buffered its porphyrin, provided can indirectly activate reduce stress. Even without lowering dosage, effect alleviated potent considered be hormesis-like. This “Therapeutic Brief” propose that Keywords: Hematin, radical, molecular hydrogen, Nrf2, porphyrin