A new method for relocating proteins that have been misplaced in cells could mean new treatments for cancers and neurodegeneration.
Cells are highly controlled spaces that rely on every protein being in the right place. Many diseases, including cancers and neurodegenerative disorders, are associated with misplaced proteins. In some cancers, for instance, a protein that normally stands watch over DNA replicating in the nucleus is sent far from the DNA it is meant to monitor, allowing cancers to grow.
Sometimes, this movement makes the protein stop working altogether. Proteins that act on DNA, for instance, will not find any DNA in the cytoplasm and float off doing nothing. Other times, this movement leads to a protein becoming a bad actor. In ALS, for example, a mutation sends a certain protein, called FUS, out of the nucleus and into the cytoplasm, where it aggregates into toxic clumps and eventually kills the cell.
"Nature is inherently complex and interconnected, so it's crucial to have interdisciplinary approaches," said Ng."Borrowing logic or tools from one field to address a problem in another field often results in very exciting 'what if' questions and discoveries." The team wondered if they could build a TRAM that would mimic the protective effect of the mutation, taking the protein for a ride down to the end of the axon. Their TRAM not only moved the target protein down the axon, but also made the cell more resistant to stress that mimics neurodegeneration.
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