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PLOS Science Wednesday: Hi reddit, we’re Hui-Chen Lu, Yousuf Ali, Hunter Allen and we found that people with the NMNAT2 protein had greater resistance to cognitive decline – Ask Us Anything!
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Hi Reddit, My name is Hui-Chen Lu and I am a Professor at Indiana University Bloomington. My research focuses on how neural circuits wire up during development and how to keep neurons healthy despite various insults and with aging. The majority of neurons in the brains are born prenatally and have to stay healthy throughout our lifespan. My name is Yousuf Ali and I am an assistant scientist in Dr. Lu’s lab. My research focuses on understanding the underlying mechanisms that disrupt cellular homeostasis and serve as a basis of disease in different proteinopathies, specifically Alzheimer’s disease and tauopathies. My name is Hunter Allen and I am a research assistant in the lab of Dr. Hui-Chen Lu at Indiana University Bloomington. I currently head-up operation of our multi-photon microscope as well manage lab IT functions and assist with technical and computing activities such as Matlab, Python, and other programming for data analysis. My name is Hugo Bellen and I am a Professor at Baylor College of Medicine and a HHMI Investigator. Our research interests include neuronal communication/maintenance and development of scientific tools allowing large scale and efficient scientific discoveries. We recently published a paper titled “NMNAT2: HSP90 Complex Mediates Proteostasis in Proteinopathies” in PLOS Biology. NMNAT2, or nicotinamide mononucleotide adenylyl transferase 2, is becoming recognized as a key neuronal maintenance factor. By examining NMNAT2 levels in brains donated by more than 500 elderly people whose cognitive function was tested annually before death, we found higher levels of NMNAT2 in people who had greater resistance to cognitive decline. People with lower NMNAT2 were more likely to suffer from dementia, suggesting that the protein helps preserve neurons related to learning and memory. NMNAT2 exerts both an enzyme function to protect neurons from stress caused by over-excitation, and a ‘chaperone’ function to combat the misfolded proteins produced in the brain during aging. Many neurodegenerative disorders are caused by accumulation of “misfolded” proteins that “clump up” in the brain in forms often referred to as “plaques,” or “tangles.” Using mouse and cell culture models, we found that NMNAT2 act as a molecular chaperone and binds to misfolded proteins to prevent or repair the errors that cause these clumps. Interestingly, its enzymatic function is required to defend against excitotoxicity. Our work here suggests that NMNAT2 uses both its chaperone and enzymatic functions to combat different neuronal insults in a context-dependent manner. We will be answering your questions at 1pm ET – Ask Us Anything!