Protein disaggregation machineries in the human cytosol

Proteins carry out the vast majority of functions in cells, but can only do so when properly folded. Following stress or mutation, proteins can lose their proper fold, resulting in misfolding, inactivity, and aggregation–posing a threat to cellular health. In order to counteract protein aggregation, cells have evolved a remarkable subset of molecular chaperones, called protein disaggregases, which collaboratively possess the ability to forcibly untangle protein aggregates. Here, we review the different chaperone disaggregation machineries present in the human cytosol and their mechanisms of action. Understanding, how these disaggregases function, is both universally and clinically important, as protein aggregation has been linked to multiple, debilitating neurodegenerative diseases.