Scientists Discover “Master Key” Protein for Stronger Memory and Learning

Research led by Rutgers suggests there could be significant new possibilities for treating neurodegenerative diseases and brain injuries.

Researchers have uncovered how a specific protein supports the stability of connections between brain cells, which are essential for learning and memory.

According to the scientists, their findings, published in the journal Science Advances, may lead to new therapeutic strategies for treating traumatic brain injuries and neurological conditions like Parkinson’s and Alzheimer’s.

Cypin’s role in healthy synaptic function

A research team led by a professor at Rutgers University–New Brunswick has identified a newly discovered function of cypin, a protein found in the brain. The team found that cypin increases the tagging of certain proteins located at synapses, the small junctions where neurons send and receive signals. These molecular tags help direct the proteins to their correct locations, which is essential for proper synaptic activity.

According to the researchers, this discovery could have significant implications for developing treatments for various brain disorders.

“Our research indicates that developing treatments or therapies that specifically focus on the protein cypin may help improve the connections between brain cells, enhancing memory and thinking abilities,” said Bonnie Firestein, a Distinguished Professor in the Department of Cell Biology and Neuroscience in the School of Arts and Sciences and an author of the study. “These findings suggest that cypin could be used to develop treatments for neurodegenerative and neurocognitive diseases, as well as brain injuries.”

How cypin stabilizes brain communication

For over twenty years, Firestein has focused her research on cypin, a brain protein with critical roles in maintaining neural function. Her most recent findings reveal several key insights into how cypin operates and why it matters for brain health.

One major discovery is that cypin plays a role in attaching specific molecular tags to proteins at synapses, the sites where neurons communicate. These tags help position the proteins correctly, ensuring they can transmit signals efficiently. Accurate tagging and protein placement are vital for neurons to function properly.

Another key finding shows that cypin interacts with the proteasome, a protein complex that breaks down unneeded or damaged proteins. When cypin binds to the proteasome, it slows down this degradation process, allowing certain proteins to accumulate. This buildup can enhance several cellular processes that support effective communication between brain cells.

Strengthening memory through synaptic support

Firestein’s research also shows that when there is more cypin present, the levels of important proteins in the synapses increase. These proteins are vital for effective communication between neurons, empowering learning and memory.

Additionally, cypin increases the activity of another protein called UBE4A, which also helps with the tagging process. This indicates that cypin’s influence on synaptic proteins is partly because of its effect on UBE4A.

The work highlights the importance of cypin in maintaining healthy brain function and its potential as a target for therapeutic interventions.

“Even though this study is what we call ‘basic research,’ it eventually can be applied in practical, clinical settings,” said Firestein, who already is conducting such “translational” work in parallel. Translational research is a type of research that takes discoveries made in the lab and turns them into practical treatments or solutions to improve human health.

Cypin’s significant role in the workings of the brain’s synapses makes it highly relevant to the potential treatment of neurodegenerative diseases and traumatic brain injury, she said. For example, healthy synaptic function is often disrupted in diseases such as Alzheimer’s and Parkinson’s.

In addition, the protein’s role in promoting synaptic plasticity – the ability of synapses to strengthen or weaken over time – means it may be used to help counteract the synaptic dysfunction seen in neurodegenerative diseases and brain injuries.

Reference: “Cypin regulates K63-linked polyubiquitination to shape synaptic content” by Srinivasa R. Gandu, Ana R. Rodriguez, Jared Lamp, Mihir V. Patel, Kiran Madura, Irving E. Vega and Bonnie L. Firestein, 11 July 2025, Science Advances.
DOI: 10.1126/sciadv.ads5467

The study was supported in part by the National Institutes of Health (NINDS), the Coalition for Brain Injury Research, a charitable foundation dedicated to the memory of Dennis John Benigno, who suffered a traumatic brain injury in junior high school; and private donors Jamuna Rajasingham and Dyan Rajasingham.

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