New technique offers closer look at brain’s distinct proteins

Work by a team led by Northwestern University (Evanston, IL) and the University of Pittsburgh (Pittsburgh, PA) is pushing toward a better understanding of the brain’s distinct proteins. This could lead to the development of new, more effective treatments for Parkinson’s, Alzheimer’s, and other such neurological diseases.

In their study, the researchers designed a virus to send an enzyme to a precise location in the brain of a living mouse. The enzyme—derived from soybeans—served to genetically tag neighboring proteins in a predetermined location. According to the researchers, they imaged the brain with fluorescence and electron microscopy, which produced a snapshot of the entire set of proteins (or proteome) inside living neurons; this was then analyzed postmortem via mass spectroscopy.

“The virus essentially acts as a message that we deliver,” says the study’s senior author Yevgenia Kozorovitskiy, the Soretta and Henry Shapiro Research Professor of Molecular Biology and associate professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences. “In this case, the message carried this special soybean enzyme. Then, in a separate message, we sent the green fluorescent protein to show us which neurons were tagged. If the neurons are green, then we know the soybean enzyme was expressed in those neurons.”

As a result of this study, which involved chemically tagging proteins and their neighbors, the researchers are now able to see how proteins work “within a specific, controlled area and how they work with one another in a proteome.”

According to the researchers, it is possible to amplify and sequence genes and RNA to identify their specific building blocks. However, this cannot be done the same way for proteins. Instead, they note, proteins must be divided into peptides and then put back together—a “slow and imperfect process.”

The team’s recent findings could help researchers to better understand and develop new treatments for neurological illnesses. Reference: V. Dumrongprechachan et al., Nat. Commun., 12, 4855 (2021); doi.org/10.1038/s41467-021-25144-y.