Imaging technique uncovers how copper imbalance may contribute to neurodegenerative diseases

Using a groundbreaking imaging technique, a University of Houston chemist is uncovering how copper imbalances in the body may contribute to neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS.

While the root cause of these incurable diseases remains largely unknown and existing medications only manage symptoms, researchers have long linked copper imbalances within neurons to severe neurological disorders. Tai-Yen Chen, associate professor of chemistry at UH, hopes to pinpoint the exact cellular pathways that fail, providing the foundational knowledge needed to develop future cures and guide therapeutic strategies.

Over the past decade, Chen's lab has secured more than $4 million to examine how copper regulation supports healthy brain development. His latest funding is in the form of a $2.16 million grant from the National Institute of General Medical Sciences, part of the National Institutes of Health.

This five-year grant renewal follows a roughly $1.9 million National Institute of General Medical Sciences grant awarded in 2019 that backed Chen's initial findings on cellular copper homeostasis. Recently published in Nature Communications, that discovery challenged a long-standing view of how a key transport protein, CTR1, works - opening new questions about how copper regulation influences cell function and development.

We discovered that a protein called CTR1, which brings copper into cells, is much more dynamic than scientists previously thought. We found that when copper levels become too high, CTR1 changes its structure in a way that helps reduce copper uptake. This appears to be an important mechanism that cells use to maintain healthy copper levels."

Tai-Yen Chen, associate professor of chemistry, University of Houston

This new grant will allow Chen's team to investigate how this copper-regulating behavior is connected to signaling in human neurons and how disruptions in this process may contribute to neurodegenerative disease.

Using advanced imaging tools developed in Chen's lab, the team can watch and measure individual CTR1 protein complexes inside individual cells. This allows researchers to see differences from cell to cell and detect rare protein behaviors that may be hidden when scientists only measure large groups of cells at once.

Traditional biochemical methods are powerful for measuring overall trends, but they usually report an average signal from many cells and many proteins. That averaging can make it difficult to see small differences between individual cells, unusual protein behaviors or short-lived events that may be important in disease.

Chen's single-molecule approach provides a closer look at how individual proteins behave inside living cells, giving researchers a more detailed view of copper regulation. The approach could eventually help scientists study other diseases and biological processes in which rare molecular events or differences between individual cells play an important role.

"Some neurological diseases have been pretty much unsolvable in the past because there were no effective approaches to ask these complex questions," Chen said. "Now, with our unique imaging approach, new questions can be asked quantitatively, which can provide insight and move the field forward."