Researchers, for the first time, have come up with a new and successful approach to identify the proteins inside different types of neurons in the brain of a living animal.
The new study which was led by Northwestern University and the University of Pittsburgh offers a giant step in understanding the brain’s millions of distinct proteins.
As the building blocks of all the cells including neurons, proteins hold keys to better understanding complex brain diseases such as Alzheimer’s and Parkinson’s, which can further lead to the development of new treatments.
Identifying proteins: What happened under the new study? |
Researchers in the new study designed a virus to send an enzyme to a precise location in the brain of a living mouse. The enzyme, derived from soybeans, genetically tagged its neighbouring proteins in a predetermined location.
The researchers after validating the technique by imaging the brain with fluorescence and electron microscopy found that their technique took a snapshot of the entire set of proteins inside the living neurons, which can then be analyzed postmortem with mass spectroscopy.
By chemically tagging the proteins and their neighbours, researchers are now able to see how the proteins work within a specific, controlled area and how they are able to work with one another in a proteome.
Along with the virus carrying the soybean enzyme, the scientists also used their virus to carry a separate green fluorescent protein.
Kozorovitskiy from Northwestern University who is also a senior author of the study stated that the virus essentially acts as a message that we deliver and in this case, the message carried this special soybean enzyme.
Then again, in a separate message, the scientists sent the green fluorescent proteins to show them which neurons were tagged. If the neurons are green, then it is understood that the soybean enzyme was expressed in those neurons.
Protein targeting lagged behind:
While genetic targeting has transformed neuroscience and biology, protein targeting has lagged behind.
Researchers are able to amplify and sequence genes and RNA to identify their exact building blocks but proteins cannot be amplified and sequenced in the same manner.
Instead, scientists have to divide the proteins into peptides and then put them back together.
However, Kozorovitskiy states that even though proteins have been out of the loop, everyone recognizes the significance of proteins as they are the ultimate effectors in the cells. Understanding where the proteins are, how they work, and how they work relative to each other is extremely important.
How identifying proteins can help in understanding brain diseases?
As the new system has been validated, the researchers will be able to apply it to mouse models for the diseases to better understand neurological illnesses.
The researchers hope to extend this approach to identify the biochemical modifications on neuronal proteins that occur during the specific patterns of brain activity or with the changes induced by the neuroactive drug to facilitate clinical advances.
Kozorovitskiy stated that the researchers look forward to taking this to the models related to brain diseases and connect those studies to the postmortem proteomics work in the human brain.
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