Abstract
A factor that is common to the most-frequent neurodegenerative diseases is the accumulation of abnormal proteins that are associated with cellular dysfunction. Contrary to years of speculation, recent evidence suggests that soluble intermediates - not the visible pathological aggregates associated with disease - are the cause of neurotoxicity. These findings suggest that aggregate formation might be an adaptive stress response that is facilitated by neuronal protein triage molecules. In particular, the molecular co-chaperone CHIP (C terminus of HSC70-interacting protein) has been linked to several of these disorders, serving as a crucial catalyst for the ubiquitination of several heat shock protein (HSP)70 client proteins that are involved in neurodegenerative disease. Therefore, understanding the mechanisms that are involved in CHIP-mediated protein trafficking might provide invaluable clues to neuronal function, both in normal and diseased conditions. © 2006 Elsevier Ltd. All rights reserved.