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ANIMAL MODEL SHEDS LIGHT ON BRAIN IRON BALANCE AND TRANSPORT |
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Dr. Esther Meyron-Holtz: Department of Biotechnology and Food Engineering, Technion- Israel Institute of Technology, Haifa. "The causative connections between pathologic iron distribution found in many common NDD (neurodegenerative diseases) and the development of neurodegeneration are still unclear. Moreover, normal iron transport and homeostasis within the brain are not completely understood. This BSF grant enables us to study the potential role of intracellular and secreted ferritin in physiological and pathological iron distribution in the brain."
Prof. Tracey Rouault: Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland "Ferritin trafficking in polarized cells is an important subject that has not yet been explored. The BSF grant helped me, in collaboration with Dr. Meyron-Holtz, to begin to study ferritin secretion, and we intend to use similar tools to investigate ferritin trafficking in neurons, which may play a significant role in neuronal iron homeostasis." |
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Brain iron balance and transport in both health and disease is not understood. Pathologic iron distribution may play a role in many NDD (neurodegenerative diseases).
Dr. Meyron-Holtz and Prof. Rouault have developed a mouse model of neurodegeneration caused by abnormalities in iron metabolism. The underlying pathology of this condition seems to be degeneration of neurons and other supporting cells in the nervous system. These include the axons -- long extensions of neurons, some of which go from the spinal cord to the extremities of the arms and legs. Their structure is maintained by pumps outside the axon that ensure the correct balance of ions (such as sodium and potassium) inside them. The energy for this process is provided by mitochondria that make ATP (energy-carrying molecule found in the cells of all living things) via pathways involving numerous iron-containing proteins.
Dr. Meyron-Holtz and Prof. Rouault discovered that oral treatment with a stable nitroxide seems to correct some of the iron-related neurodegenerative problems in their animal model. The next stage will be to test such treatment in human patients with adult-onset neurodegeneration caused by loss of iron-regulatory protein. It is hoped that this new therapy will help to alleviate the motor and other symptoms associated with this debilitating condition.
Cooperation Dr. Meyron-Holtz and Prof. Rouault have shown that mice lacking iron regulatory protein-2 develop progressive problems with movement. They become increasingly unable to reach for food and water, lose grooming ability, and may develop a tremor. In such mice, the neurons do not have enough iron due to defects in the regulation of iron import, export and storage. |
