Key Brain Protein Sheds Light on Memory Loss and Neurodegenerative Diseases

Researchers have identified how a crucial protein contributes to preserving strong connections between brain cells, essential for learning and memory.

The findings, published in the journal Science Advances, could pave the way for innovative treatments for traumatic brain injuries, Parkinson's disease, and Alzheimer's disease.

Led by a professor from Rutgers University-New Brunswick, this study revealed an unrecognized role of cypin, a protein found in the brain. The team discovered that cypin facilitates the presence of markers on specific proteins at synapses—tiny gaps where neurons communicate. These tags ensure proper positioning of proteins for optimal synapse function.

The researchers emphasized the significant implications of these findings for addressing various brain disorders.

"Our research suggests that targeting the protein cypin could enhance connections between brain cells, potentially improving memory and cognitive abilities," said Bonnie Firestein, Distinguished Professor in the Department of Cell Biology and Neuroscience at Rutgers University's School of Arts and Sciences, and an author of the study.

"These results imply that cypin might be leveraged to develop treatments for neurodegenerative diseases, neurocognitive disorders, and brain injuries."

Firestein has been studying cypin for over two decades. Her latest research uncovered important aspects of how cypin functions and why it is significant for brain health.

A key discovery is that cypin helps add specific markers to proteins in the synapses between neurons. These markers ensure the correct positioning of proteins, allowing efficient signaling.

Another critical finding is that cypin interacts with a protein complex known as the proteasome, which breaks down proteins. When cypin binds to the proteasome, it slows down this process, leading to an accumulation of proteins that positively affects various cellular functions crucial for neuron communication.

Firestein's research indicates that higher levels of cypin lead to increased levels of vital synaptic proteins, which enhance communication between neurons and promote learning and memory.

Moreover, cypin boosts the activity of a protein called UBE4A, which assists in the tagging process. This suggests that cypin influences synaptic proteins partly through its impact on UBE4A.

The study underscores the importance of cypin for maintaining healthy brain functions and highlights its therapeutic potential.

"While this research is fundamental, it has the potential to be applied in clinical settings," said Firestein. She is also conducting parallel "translational" research to convert lab discoveries into practical treatments that improve human health.

Cypin's role in brain synapses makes it highly relevant for treating neurodegenerative diseases and traumatic brain injuries, especially since synaptic function is often disrupted in conditions like Alzheimer's and Parkinson's disease. Additionally, cypin's promotion of synaptic plasticity—the ability of synapses to strengthen or weaken—suggests its potential use in counteracting the synaptic dysfunction observed in these conditions.

Other Rutgers researchers involved in the study include Kiran Madura, a professor at Robert Wood Johnson Medical School, and former doctoral students Srinivasa Gandu, Mihir Patel, and Ana Rodriguez from the Department of Cell Biology and Neuroscience. Jared Lamp and Irving Vega from Michigan State University also contributed.