http://www.nature.com/nmeth/journal/v9/n1/full/nmeth.1847.html?WT.ec_id=NMETH-201201
Erika Pastrana
Nature Methods
doi:10.1038/nmeth.1847
Published online
28 December 2011
Combining experiments and calculations makes it possible to measure the prognostic value of toxic protein species in the cell.
It is still not clear though, whether these aggregates are toxic to the cell or whether they represent a way for the cell to cope with the misfolded mutant proteins. Mutant Htt proteins are continuously shifting from one conformation to another, and it is unclear which of the conformational states (or protein species) exist at a given time in the cell and to what extent each of them contributes to the cell's degeneration.
These are not easy questions to address, and as Steven Finkbeiner and his team at the University of California, San Francisco, noted, methods for such investigations have been lacking. To date, a lot of work has focused on looking at aggregation of purified proteins in a test tube. However, “the environment in which proteins fold and misfold inside cells is very different from the one in vitro,” says Finkbeiner. The group set out to develop new tools and methods that would enable labeling the different protein species of Htt that exist in situ and estimating the pathogenic contribution of each of them.
No comments:
Post a Comment