TYK2 Enzyme Identified in the Development of Intracellular Tau Neurofibrillary Tangles

Discovery of TYK2’s Role in Tau Protein Aggregation

Role of TYK2 enzyme in producing intracellular tau protein aggregates associated with Alzheimer’s disease unveiled

Researchers at Baylor College of Medicine and collaborating institutions have uncovered the role of the enzyme tyrosine kinase 2 (TYK2) in the formation of intracellular tau protein aggregates linked to Alzheimer’s disease. This breakthrough paves the way for potential therapeutic interventions targeting tau-induced neurodegenerative disorders.

Mechanism Behind Tau Aggregation Revealed

Understanding how TYK2 and tau interact to cause aggregation

Tau protein normally binds to and stabilizes microtubules essential for the structure of nerve cell axons. However, excessive phosphorylation of tau leads to its dissociation from microtubules, spreading to neighboring cells, and forming neurofibrillary tangles (NFTs) inside cells. These NFTs are a hallmark of various neurological disorders, including Alzheimer’s disease. Previous research suggested the involvement of TYK2 in NFT development through genetic screening.

Exploration of Tau Phosphorylation by TYK2

Identification of TYK2 phosphorylation of tau at tyrosine 29

In vitro studies using human cells and transgenic mouse models expressing aggregate-forming tau revealed that TYK2 specifically phosphorylates tau at tyrosine 29. Mutating this tyrosine residue prevented tau phosphorylation by TYK2, indicating its crucial role in tau aggregation. Mice expressing a tau variant with a phosphorylation-blocking mutation at tyrosine 29 showed reduced levels of hyperphosphorylated insoluble tau, highlighting the significance of this phosphorylation site in tau accumulation.

Potential Therapeutic Implications

Exploring the use of TYK2 inhibitors for treating tau-induced dementias

Phosphorylation of tau at tyrosine 29 enhances tau stability and inhibits its clearance through cellular processes like autophagy, leading to increased aggregation. The study’s findings suggest that targeting TYK2 with existing inhibitors could hold promise for treating Alzheimer’s disease and related neurodegenerative conditions. Further research is needed to determine the efficacy of these inhibitors in reducing tau levels in the brain, setting the stage for future therapeutic developments in this area.