RT Journal Article
SR Electronic
T1 Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1292
OP 1295
DO 10.1126/science.1101738
VO 305
IS 5688
A1 Cuervo, Ana Maria
A1 Stefanis, Leonidas
A1 Fredenburg, Ross
A1 Lansbury, Peter T.
A1 Sulzer, David
YR 2004
UL http://science.sciencemag.org/content/305/5688/1292.abstract
AB Aberrant α-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates in the Lewy inclusion bodies associated with the disease. Little is known, however, about the pathways by which wild-type α-synuclein is normally degraded. We found that wild-type α-synuclein was selectively translocated into lysosomes for degradation by the chaperone-mediated autophagy pathway. The pathogenic A53T and A30P α-synuclein mutants bound to the receptor for this pathway on the lysosomal membrane, but appeared to act as uptake blockers, inhibiting both their own degradation and that of other substrates. These findings may underlie the toxic gain-of-function by the mutants.