TY - JOUR
T1 - Brain CHIP
T2 - removing the culprits in neurodegenerative disease
AU - Dickey, Chad A.
AU - Patterson, Cam
AU - Dickson, Dennis
AU - Petrucelli, Leonard
N1 - Funding Information:
L.P. is supported by NIH/NINDS funding and Institute for Study of Aging.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33845874433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845874433&partnerID=8YFLogxK
U2 - 10.1016/j.molmed.2006.11.003
DO - 10.1016/j.molmed.2006.11.003
M3 - Review article
C2 - 17127096
AN - SCOPUS:33845874433
SN - 1471-4914
VL - 13
SP - 32
EP - 38
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 1
ER -