Summary: Researchers have identified how an enzyme called TYK2 alters tau, a normal brain protein, making it accumulate and contribute to Alzheimer’s disease. The discovery, made using both human cells and animal models, suggests that partially inhibiting TYK2 might help reduce harmful tau buildup in the brain.
Journal: Nature Neuroscience, November 11, 2024, DOI: 10.1038/s41593-024-01777-2 | Reading time: 4 minutes
A Protein’s Jekyll and Hyde Transformation
Inside our brains, a protein called tau normally plays a vital role in maintaining healthy brain function. But in Alzheimer’s disease and dozens of other neurological conditions, tau can transform into a destructive force. Now, researchers have discovered how this transformation occurs.
“Many studies have shown that the accumulation of tau in neurons and glial cells in the brain is a main characteristic of Alzheimer’s disease and at least 24 more neurological diseases,” said Dr. Ji-Yoen Kim, assistant professor of molecular and human genetics at Baylor College of Medicine.
Unraveling the Mystery
The research team found that an enzyme called TYK2 chemically modifies tau by adding phosphate groups at a specific location. This seemingly small change has major consequences.
“We found that TYK2 adds phosphate groups to tau at a particular location on the protein identified as Tyrosine 29,” Kim explained. “This modification stabilizes tau levels in human cells and mouse neurons by making it resistant to autophagy, a cellular process important for clearing proteins.”
From Discovery to Potential Treatment
The findings, published in Nature Neuroscience, open up new possibilities for treatment. When researchers partially reduced TYK2 in two different mouse models, they observed decreased tau levels and reduced accumulation.
“Although much work is needed, our findings suggest that partial inhibition of TYK2 could thus be a strategy to reduce tau accumulation and toxicity,” Kim noted. “To this end, we are encouraged by the fact that others have developed TYK2 inhibitors that have been tested in humans for other indications,” added Dr. Huda Zoghbi, director of the Duncan NRI.
Glossary
- Tau: A protein normally involved in maintaining brain cell structure
- TYK2: An enzyme that modifies proteins by adding phosphate groups
- Autophagy: The body’s process for breaking down and recycling cellular components
- Phosphate groups: Chemical modifications that can change how proteins behave
Quiz
- What enzyme transforms tau into its harmful form?
Answer: TYK2 - Where does TYK2 add phosphate groups to tau?
Answer: Tyrosine 29 - How many neurological diseases involve tau accumulation?
Answer: At least 24 - What happened when researchers reduced TYK2 in mouse models?
Answer: Tau levels decreased and accumulation was reduced
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