Unveiling the Surprising Duality of Protein: A Shield Against Brain Damage
A groundbreaking study from Johns Hopkins Medicine reveals a fascinating dual role of the enzyme biliverdin reductase A (BVRA), showcasing its ability to protect neurons from oxidative stress. This discovery challenges our understanding of BVRA's function, as it was previously known for producing the yellow pigment bilirubin. The research, funded by the National Institutes of Health, was published in the prestigious journal Proceedings of the National Academy of Sciences.
The study, led by Bindu Paul, M.S., Ph.D., an associate professor at Johns Hopkins University School of Medicine, highlights BVRA's role in safeguarding brain cells from oxidative stress. This stress, a common feature of neurodegenerative diseases like Alzheimer's, occurs when there's an imbalance between oxidants and antioxidants. By modulating the protein NRF2, BVRA ensures the production of protective proteins and antioxidants, effectively countering oxidative damage.
The research team's findings are particularly intriguing. When they genetically engineered mice to lack both BVRA and NRF2 proteins, the mice couldn't survive, suggesting a critical interaction between these proteins. In mice lacking only BVRA, NRF2 malfunctioned, leading to reduced antioxidant production. In cell cultures, BVRA and NRF2 were shown to physically bind, regulating genes involved in neuron protection, including those related to oxygen transport, immune signaling, and mitochondrial function.
The study's most remarkable aspect is that BVRA's protective function doesn't rely on its bilirubin production. The team created BVRA mutants that couldn't produce bilirubin, but these mutants still effectively regulated NRF2 and protected neurons in mice. This discovery challenges the notion that BVRA's primary role is bilirubin production, instead revealing its significance as a molecular integrator in cellular defense.
Chirag Vasavda, M.D., Ph.D., a physician and former Johns Hopkins M.D./Ph.D. student, emphasizes the broader implications of this research. "This work demonstrates that BVRA is more than just a bilirubin producer; it's a key player in neuronal protection." Ruchita Kothari, a graduate student and co-first author, adds, "Our research highlights the long-term value of understanding the intricate mechanisms of cellular defense."
Looking ahead, Paul's team plans to investigate how the BVRA-NRF2 connection is disrupted in Alzheimer's disease models. This research not only sheds light on the complex mechanisms of neuroprotection but also opens up new avenues for therapeutic interventions, potentially slowing the progression of neurodegenerative disorders.
