Study Provides New Avenues for Treatment in Neurodegeneration

The study, led by Changyi Ji, describes the mechanism by which neurons manage the essential trace element iron.

It also describes how the mechanism likely contributes to neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease.

Ji is a doctoral candidate in the lab of Daniel J. Kosman, PhD, SUNY Distinguished Professor of biochemistry.

Iron, a trace element for neuronal development, is vital for enzymes. Enzymes use iron for energy metabolism and neurotransmitter synthesis in neurons. 

Dysregulation of neuronal iron homeostasis correlates with reactive oxygen species production and protein aggregation, where the impacted brain regions show cell damage and neural degeneration. 

In brain interstitial fluid, transferrin-bound iron (TBI) and non-transferrin-bound iron (NTBI) exist as potential iron sources. 

Until this research, the iron uptake transporters in neurons for NTBI, a major iron source for neural cells, had not been identified, nor their mechanism of action explained.

The article, “Molecular Mechanisms of Non-Transferrin-Bound and Transferring-Bound Iron Uptake in Primary Hippocampal Neurons,” characterized the first step of iron trafficking in neurons. It was co-authored by Kosman, Ji’s mentor.

Their study quantified the expression of key proteins involved in the iron trafficking process. Doing so provided Ji and Kosman with biochemical evidence for how these key proteins were linked to supplying iron to these cells. 

The article appeared in a June 2015 issue of the journal, which featured one of Ji’s data figures as a cover illustration.

Using cultured primary rat hippocampal neurons, the researchers identified which iron-uptake proteins were expressed in those cells and then established their roles in iron uptake. 

Radiolabeled iron-59 was used to obtain the kinetic behavior of iron uptake into neurons. 

Ji and Kosman correlated the results of this functional assay to the presence or absence of proteins and pathways likely to be involved in iron accumulation. 

These results were also correlated with the subcellular localization of these candidate proteins to assess which of these proteins contributed to neuronal iron accumulation from different iron sources. 

“Working in Dr. Kosman’s lab is a great experience. It brought my interests to an interdisciplinary field between metal biology and neuroscience. With his help and advice, I had opportunities to present my work at conferences and publish in a scientific journal,” said Ji.

A former participant of the CLIMB-HI Program, Ji has presented her work at a Gordon Research Conference, “Cell Biology of Metals,” and a Federation of American Societies for Experimental Biology conference, “Trace Elements in Biology and Medicine.”

The CLIMB-HI Program is a two-year professional development program for doctoral students that introduces them to skills they will need as professional scientists.