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Maciej J. Stawikowski, Ph.D., lead author and assistant professor of chemistry and biochemistry in FAU’s Charles E. Schmidt College of Science.
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Credit: Florida Atlantic University
The quest for solutions for Alzheimer’s disease and other neurodegenerative disorders remains one of the most pressing goals in brain research. According to Maciej J. Stawikowski, Ph.D., assistant professor of chemistry and biochemistry at Florida Atlantic University (FAU), the key may lie in understanding how cholesterol and other lipids move through cells and how they impact on their communication.
“It’s well known that lipids are linked to Alzheimer’s disease,” says Stawikowski, a member of FAU’s Stiles-Nicholson Brain Institute. “A lipid imbalance can lead to the formation of amyloid plaques – large clumps of proteins that disrupt cellular function, a hallmark of Alzheimer’s. »
His team, including Qi Zhang, Ph.D., associate professor in FAU’s Department of Chemistry and Biochemistry, focused on developing advanced tools to explore the relationship between lipids and cellular function.
Cholesterol is an essential component of cell membranes, enabling hormone production, membrane stability and signaling. However, disruptions in the movement of cholesterol between cellular compartments may play a role in Alzheimer’s disease and other neurodegenerative diseases. To study this phenomenon, Stawikowski and his team designed fluorescent cholesterol probes (CNDs) intended to track cholesterol within cell membranes.
A new study, published in Scientific Reportsdemonstrates how CND probes can help visualize cholesterol in living cells. By combining computer simulations and live cell imaging, the researchers shed light on how different probe designs influence the behavior of cholesterol probes.
These innovative probes could deepen our understanding of how cholesterol imbalances contribute to Alzheimer’s disease and other neurodegenerative disorders. By understanding the role of cholesterol in the formation of amyloid plaques and cell signaling, researchers could develop drugs to modulate lipid activity, thus paving the way for new treatments or preventive strategies.
“With these probes, we can now visualize the movement and distribution of cholesterol in living cells with an unprecedented level of detail,” says Stawikowski, lead author of the study.
-CND probes are designed using a 1,8-naphthalimide (ND) scaffold, known for its unique fluorescent properties, including large Stokes shifts and sensitivity to environmental changes. This innovative concept allows for modular customization, giving researchers the opportunity to adjust probes with different polyfunctional groups and linkages to meet specific experimental requirements. The results show that modifying functional groups or linkages could improve the sensitivity and targeting ability of probes.
These probes are classified into three distinct types. Neutral probes tend to aggregate easily, but their uptake by cells is limited. In contrast, loaded probes show improved solubility and better interaction with cell membranes. Probes containing hydroxyl groups further strengthen hydrogen bonds and lipid interactions, making them particularly effective for studying membrane behavior.
Additionally, some variants of CND probes are pH sensitive, allowing researchers to track the movement of cholesterol in organelles with varying acidity levels, such as lysosomes and lipid droplets. Compared to traditional cholesterol probes, these tools offer better fluorescent properties and more precise monitoring of cholesterol dynamics, providing deeper insights into cellular processes.
“Cholesterol is essential for brain function, but its dysregulation could be a key factor in disease progression,” says Stawikowski. “Our new tools provide insight into how cholesterol impacts cellular processes and could help identify therapeutic targets for conditions like Alzheimer’s.” »
The research team’s fluorescent cholesterol probes offer applications beyond Alzheimer’s disease, with potential uses in membrane biology, lipid dynamics and drug delivery. By combining experimental techniques and computer simulations, the FAU team laid the foundation for developing better fluorescent cholesterol probes that can be used to study a wide range of lipid-related disorders.
These probes are versatile tools that can be adapted to diverse research needs, marking a major advancement in understanding the role of cholesterol in cellular health and disease.
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About Florida Atlantic University:
Established in 1961, Florida Atlantic University opened in 1964 as Florida’s fifth public university. Today, it serves more than 30,000 undergraduate and graduate students on six campuses along Florida’s southeast coast. In recent years, the university has doubled its spending on research and surpassed its peers in student success. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps disappear. Designated as a Hispanic-serving institution, it is ranked among the best public universities by U.S. News & World Report and has high research activity according to the Carnegie Foundation for the Advancement of Teaching.
Research on cholesterol and its implications in complex diseases such as Alzheimer’s poses an interesting framework for considering new therapeutic strategies. Although the links between lipids and brain health are established, exploring the visualization tools developed by FAU researchers could open up new horizons. In the future, this approach could not only help target cholesterol in neurodegenerative diseases, but also shed light on avenues for other pathologies, and challenge our current understanding of the interaction between lipids and cellular processes.
Good to know: Research into cholesterol and its effects on health is a rapidly expanding field, with potentially revolutionary implications in the development of treatments for various diseases, particularly neurodegenerative ones.
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