Brain CHIP: removing the culprits in neurodegenerative disease.
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.
Dickey
Chad A
CA
Division of Neuroscience, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA.
Patterson
Cam
C
Dickson
Dennis
D
Petrucelli
Leonard
L
D000367:Age Factors; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology; D021381:Protein Transport / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases