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2013 Grants - Moreira
Mitochondrial Trafficking In Alzheimer Disease: Revealing the Role of HUMMR
Paula Moreira, Ph.D.
Center for Neuroscience and Cell Biology
2013 New Investigator Research Grant
Mitochondria are cellular components that normally provide energy and nutrients to the cell. They also help ensure the health of synapses, the tiny spaces through which brain cells communicate. During Alzheimer's disease, however, many mitochondria lose their ability to move around the cell and carry out normal functions. This lack of mobility and function may lead to synaptic damage, declines in cognition (brain function) and other Alzheimer's-related changes. Yet the exact nature of mitochondrial damage in Alzheimer's remains unclear.
In preliminary studies, Paula Moreira, Ph.D., and colleagues have found that a protein called hypoxia up-regulated mitochondrial movement regulator (HUMMR) helps facilitate the movement of mitochondria in healthy brains. Though the role of HUMMR in Alzheimer's disease is unknown, the researchers hypothesize that brain levels of this protein become reduced in Alzheimer's. Loss of HUMMR may prevent other proteins called kinesins to move mitochondria around the cell's axons—the arm-like extensions that send out and receive chemical messages. Loss of mitochondrial function in axons likely promotes synaptic damage and cognitive loss.
For their current grant, Dr. Moreira and colleagues will test this hypothesis in cultured brain cells, in autopsied brain samples from people who had Alzheimer's disease and in mice genetically engineered to develop Alzheimer's-like brain changes. The researchers will use various methods to alter HUMMR levels in the cells and engineered mice. They will then determine how changing these protein levels affects mitochondrial activity. They will also test their mice to see if altered HUMMR expression affects the animals' cognitive abilities. Overall, the results of this work could establish HUMMR as a novel target for moderating dementia-related cognitive decline in humans.