In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2022-12-27), p. e0278130-
Kurzfassung:
Huntington’s disease is an autosomal dominant heritable disorder caused by an expanded CAG trinucleotide repeat at the N-terminus of the Huntingtin ( HTT ) gene. Lowering the levels of soluble mutant HTT protein prior to aggregation through increased degradation by the proteasome would be a therapeutic strategy to prevent or delay the onset of disease. Native PAGE experiments in Hdh Q150 mice and R6/2 mice showed that PA28αβ disassembles from the 20S proteasome during disease progression in the affected cortex, striatum and hippocampus but not in cerebellum and brainstem. Modulating PA28αβ activated proteasomes in various in vitro models showed that PA28αβ improved polyQ degradation, but decreased the turnover of mutant HTT. Silencing of PA28αβ in cells lead to an increase in mutant HTT aggregates, suggesting that PA28αβ is critical for overall proteostasis, but only indirectly affects mutant HTT aggregation.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0278130
DOI:
10.1371/journal.pone.0278130.g001
DOI:
10.1371/journal.pone.0278130.g002
DOI:
10.1371/journal.pone.0278130.g003
DOI:
10.1371/journal.pone.0278130.g004
DOI:
10.1371/journal.pone.0278130.g005
DOI:
10.1371/journal.pone.0278130.s001
DOI:
10.1371/journal.pone.0278130.s002
DOI:
10.1371/journal.pone.0278130.s003
DOI:
10.1371/journal.pone.0278130.s004
DOI:
10.1371/journal.pone.0278130.s005
DOI:
10.1371/journal.pone.0278130.s006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2267670-3
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