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Exploring the Role of Iron in Multiple System Atrophy

Exploring the Role of Iron in Multiple System Atrophy. Jay Shukla Dr. Erin McAllum Dr. Gawain McColl Prof. David Finkelstein. Iron in our Brains – A Double Edged Sword.

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Exploring the Role of Iron in Multiple System Atrophy

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  1. Exploring the Role of Iron in Multiple System Atrophy Jay Shukla Dr. Erin McAllum Dr. Gawain McColl Prof. David Finkelstein

  2. Iron in our Brains – A Double Edged Sword Iron (Fe) is essential bio-metal for normal functioning of cells in the body and the brain – Iron deficiency during infancy and childhood results into impaired brain development Iron participates in energy producing reactions that fuels neuronal cells However, excess of iron can give rise to oxidative stress and damage neuronal cells Hence, iron levels need to be properly maintained in brain to prevent it from participating in toxic reactions

  3. Iron and Neurodegeneration There is emerging evidence of increased brain iron in neurodegenerative disorders like Parkinson’s disease, Alzheimer’s disease, etc. Increased iron levels reported in MSA brains, especially in putamen This elevated iron could participate in neuronal loss in MSA Moreover, iron can promote aggregation of α-synuclein, the protein that accumulates in MSA brains, and contribute to disease progression in MSA There are drugs available that can be used to remove excess iron from brain to treat MSA but, they need to be tested first in a mouse model

  4. Our Study and Findings Changes in brain iron levels in MSA mouse models have not been studied Hence, we wanted to measure iron levels in different brain regions of a well-studied mouse model of MSA, the PLP-αsyn model We found increased iron levels in substantia nigra and cerebellumof the PLP-αsyn mice. In addition, our results point towards improper iron storage in these mice. Currently, we are treating these mice with a drug that can mop-up excess of iron from brain (anti-iron drug) and see if the drug makes these mice better. If successful, this drug has the potential to quickly translate into MSA human trials

  5. Thank You! • We would like to acknowledge for: • A seed grant in 2017 that funded our drug trial in the mouse model of MSA • A Young Investigator Travel Award in 2019 to Mr. Jay Shukla, the PhD student working on this project to present his results at the 14th International Conference on Alzheimer’s and Parkinson’s diseases in Lisbon, Portugal

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