Proteostasis

This biological machinery controlling the folding and function environment of the cell is referred to as the proteostasis network and is central for life. ❋ Unknown (2009)

Based on earlier studies of the folding environment required for CFTR function published in the journal Cell, the scientists reasoned that altering HDAC function might also rebalance proteostasis networks in the cell to favor functional restoration. ❋ Unknown (2009)

"By rebalancing the proteostasis program to provide a more supportive cellular environment," said Balch, "the cells appear to treat the mutation more like a polymorphism [genetic differences that are responsible for individual diversity] rather than something dangerous needing to be completely eliminated." ❋ Unknown (2009)

This feature is reminiscent of its potential mechanism of action, Balch said, perhaps involving chromatin remodeling leading to an altered, protective proteostasis environment in the lung cell that could be sustainable. ❋ Unknown (2009)

Using a bioinformatics approach led by the Gerard Manning laboratory at the Salk Institute of Biological Sciences, the team showed that the compound increased the functioning of mutated CFTR proteins at multiple levels in the proteostasis network. ❋ Unknown (2009)

Rather than attempting to directly target or replace the mutant CFTR proteins present in cystic fibrosis patients-an approach that had so far failed to yield dramatic new treatments for the DF508 disease-Balch and colleagues sought instead to adjust the cell folding or maintenance proteostasis machinery of the cell to make a new cellular environment that would ❋ Unknown (2009)

The proper folding of proteins in cells, or proteostasis, is important for health. ❋ Unknown (2009)

These problems and consequences on cellular proteostasis may lead to disease. ❋ Unknown (2009)

"By rebalancing the proteostasis program to provide a more supportive cellular environment," said Balch, "the cells appear to treat the mutation more like a polymorphism ❋ Unknown (2009)

This Recovery Act funding provides an opportunity to better understand the role of proteostasis and the aging environment in which protein misfolding occurs, "said NIA's Sierra. ❋ Unknown (2009)