Newswise — Protein aggregates progressively accumulate as individuals age and have been strongly linked to neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's disease. However, the precise role of these aggregates in the development of these diseases remains uncertain.
In a groundbreaking study conducted by the Nyström lab at Gothenburg University, in collaboration with the Max Planck Institute for Biology of Ageing in Germany, a novel technique has been developed to manipulate protein aggregates spatially. This innovative approach has been successfully applied to both budding yeast, a widely used model organism, and human cells.
The research team, led by Professor Thomas Nyström, managed to engineer a method that allows for the targeted removal of protein aggregates from cells. Their findings, which have been published in the esteemed journal Nature Communications, showcase the initial implementation of this technique in budding yeast and its subsequent adaptation for use in human cells.
Free of protein aggregates
The researchers devised a synthetic cellular export system by combining an aggregate-binding protein with a daughter-cell-targeting factor. This clever fusion allowed for the separation of protein aggregates from the mother cell as the daughter cell formed, ensuring that the mother cell remained free of aggregates.
Remarkably, this approach proved successful in addressing not only endogenous protein aggregates that accumulate with age but also mutant Huntingtin aggregates associated with Huntington's disease. Through the daughter targeting system, the team demonstrated that exporting mutant Huntingtin protected yeast mother cells from cell death. These findings provide compelling evidence suggesting that large Huntingtin aggregates may indeed be highly toxic and contribute to the progression of the disease, a matter that has been the subject of extensive debate.
Potential future therapy
Dr. Arthur Fischbach, the postdoctoral researcher and lead author of the study, expressed the significance of their work by stating, "To our knowledge, this is the first demonstration of the controlled and engineered export of protein aggregates from cells. It is also plausible that our targeting system can be adapted to export other forms of cellular damage." Dr. Fischbach highlights the potential future implications of their findings, suggesting that the approach they developed, known as the Aggregate Targeting System (ATS), could potentially serve as a novel therapeutic strategy for neurodegenerative diseases. Although supporting data is currently lacking, Dr. Fischbach emphasizes the urgent need for innovative therapies in this field and believes that the ATS concept could contribute to a deeper understanding of these devastating conditions.
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