Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 서혜명 | - |
dc.date.accessioned | 2023-07-24T01:55:12Z | - |
dc.date.available | 2023-07-24T01:55:12Z | - |
dc.date.issued | 2008-10 | - |
dc.identifier.citation | Human Molecular Genetics, v. 17, NO. 20, Page. 3144-3153 | - |
dc.identifier.issn | 0964-6906;1460-2083 | - |
dc.identifier.uri | https://academic.oup.com/hmg/article/17/20/3144/593977 | en_US |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/184282 | - |
dc.description.abstract | Intraneuronal protein aggregates of the mutated huntingtin in Huntington's disease (HD) brains suggest an overload and/or dysfunction of the ubiquitin-proteasome system (UPS). There is a general inhibition of the UPS in many brain regions (cerebellum, cortex, substantia nigra and caudate-putamen) and skin fibroblasts from HD patients. In the current experiment, the widely used mutant huntingtin-exon 1 CAG repeat HD transgenic mice model (R6/2) (with 144 CAG repeat and exon 1) during late-stage pathology, had increases in proteasome activity in the striatum. However, this discrepancy with HD patient tissue was not apparent in the mutant CAG repeat huntingtin full-length HD (YAC72) transgenic mouse model during post-symptomatic and late-stage pathology, which then also showed UPS inhibition similar to HD patients' brains. In both types of HD model mice, we determined biochemical changes, including expression of brain-derived neurotrophic factor (BDNF) and mitochondrial complex II/III (MCII/III) activities related to HD pathology. We found increases of both BDNF expression, and MCII/III activities in YAC72 transgenic mice, and no change of BDNF expression in R6/2 mice. Our data show that extreme CAG repeat lengths in R6/2 mice is paradoxically associated with increased proteasome activity, probably as a cellular compensatory biochemical change in response to the underlying mutation. Changes in HD patients for UPS function, BDNF expression and MCII/III activity are only partially modeled in R6/2 and YAC72 mice, with the latter at 16 months of age being most congruent with the human disease. | - |
dc.description.sponsorship | National Institutes of Health (NS-30064 to O.I.), Vaughan Foundation (to O.I.), KOSEF (R01-2007-000-20135-0 to H.S.) and Hanyang University (HYU-2005 to H.S.) | - |
dc.language | en | - |
dc.publisher | Oxford University Press | - |
dc.title | Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patients | - |
dc.type | Article | - |
dc.relation.no | 20 | - |
dc.relation.volume | 17 | - |
dc.identifier.doi | 10.1093/hmg/ddn211 | - |
dc.relation.page | 3144-3153 | - |
dc.relation.journal | Human Molecular Genetics | - |
dc.contributor.googleauthor | Seo, Hyemyung | - |
dc.contributor.googleauthor | Kim, Woori | - |
dc.contributor.googleauthor | Isacson, Ole | - |
dc.sector.campus | E | - |
dc.sector.daehak | 과학기술융합대학 | - |
dc.sector.department | 의약생명과학과 | - |
dc.identifier.pid | hseo | - |
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