TY - JOUR
T1 - The Ubiquitin-Proteasome System in Huntington's Disease: Are Proteasomes Impaired, Initiators of Disease, or Coming to the Rescue?
AU - Schipper-Krom, Sabine
AU - Juenemann, Katrin
AU - Reits, Eric A. J.
PY - 2012
Y1 - 2012
N2 - Huntington's disease is a progressive neurodegenerative disease, caused by a polyglutamine expansion in the huntingtin protein. A prominent hallmark of the disease is the presence of intracellular aggregates initiated by N-terminal huntingtin fragments containing the polyglutamine repeat, which recruit components of the ubiquitin-proteasome system. While it is commonly thought that proteasomes are irreversibly sequestered into these aggregates leading to impairment of the ubiquitin-proteasome system, the data on proteasomal impairment in Huntington's disease is contradictory. In addition, it has been suggested that proteasomes are unable to actually cleave polyglutamine sequences in vitro, thereby releasing aggregation-prone polyglutamine peptides in cells. Here, we discuss how the proteasome is involved in the various stages of polyglutamine aggregation in Huntington's disease, and how alterations in activity may improve clearance of mutant huntingtin fragments
AB - Huntington's disease is a progressive neurodegenerative disease, caused by a polyglutamine expansion in the huntingtin protein. A prominent hallmark of the disease is the presence of intracellular aggregates initiated by N-terminal huntingtin fragments containing the polyglutamine repeat, which recruit components of the ubiquitin-proteasome system. While it is commonly thought that proteasomes are irreversibly sequestered into these aggregates leading to impairment of the ubiquitin-proteasome system, the data on proteasomal impairment in Huntington's disease is contradictory. In addition, it has been suggested that proteasomes are unable to actually cleave polyglutamine sequences in vitro, thereby releasing aggregation-prone polyglutamine peptides in cells. Here, we discuss how the proteasome is involved in the various stages of polyglutamine aggregation in Huntington's disease, and how alterations in activity may improve clearance of mutant huntingtin fragments
U2 - https://doi.org/10.1155/2012/837015
DO - https://doi.org/10.1155/2012/837015
M3 - Article
C2 - 23050151
SN - 2090-2255
VL - 2012
SP - 837015
JO - Biochemistry Research International
JF - Biochemistry Research International
ER -