Unknown

Dataset Information

0

Proteasome activator enhances survival of Huntington's disease neuronal model cells.


ABSTRACT: In patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' skin fibroblasts or mutant huntingtin-expressing striatal neurons. Following compromise of the UPS, overexpression of the proteasome activator subunit PA28gamma, but not subunit S5a, recovered proteasome function in the HD cells. PA28gamma also improved cell viability in mutant huntingtin-expressing striatal neurons exposed to pathological stressors, such as the excitotoxin quinolinic acid and the reversible proteasome inhibitor MG132. These results demonstrate the specific functional enhancements of the UPS that can provide neuroprotection in HD cells.

SUBMITTER: Seo H 

PROVIDER: S-EPMC1800909 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Proteasome activator enhances survival of Huntington's disease neuronal model cells.

Seo Hyemyung H   Sonntag Kai-Christian KC   Kim Woori W   Cattaneo Elena E   Isacson Ole O  

PloS one 20070228 2


In patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' ski  ...[more]

Similar Datasets

| S-EPMC4949444 | biostudies-literature
| S-EPMC7181660 | biostudies-literature
| S-EPMC5525749 | biostudies-literature
| S-EPMC4686214 | biostudies-literature
| S-EPMC5124744 | biostudies-literature
| S-EPMC3653299 | biostudies-literature
| S-EPMC4720898 | biostudies-literature
| S-EPMC8727874 | biostudies-literature
| S-EPMC4064471 | biostudies-literature
| S-EPMC6063913 | biostudies-literature