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 Field | Value | Language |
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dc.contributor.author | Seo, Hyemyung | - |
dc.contributor.author | Kim, Woori | - |
dc.contributor.author | Isacson, Ole | - |
dc.date.accessioned | 2021-06-23T17:04:01Z | - |
dc.date.available | 2021-06-23T17:04:01Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2008-10 | - |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/42105 | - |
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.language | 영어 | - |
dc.language.iso | 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.contributor.affiliatedAuthor | Seo, Hyemyung | - |
dc.identifier.doi | 10.1093/hmg/ddn211 | - |
dc.identifier.scopusid | 2-s2.0-53349101055 | - |
dc.identifier.wosid | 000259766800005 | - |
dc.identifier.bibliographicCitation | Human Molecular Genetics, v.17, no.20, pp.3144 - 3153 | - |
dc.relation.isPartOf | Human Molecular Genetics | - |
dc.citation.title | Human Molecular Genetics | - |
dc.citation.volume | 17 | - |
dc.citation.number | 20 | - |
dc.citation.startPage | 3144 | - |
dc.citation.endPage | 3153 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | YAC128 MOUSE MODEL | - |
dc.subject.keywordPlus | MUTANT HUNTINGTIN | - |
dc.subject.keywordPlus | NEURONAL DEATH | - |
dc.subject.keywordPlus | SELECTIVE DEGENERATION | - |
dc.subject.keywordPlus | 3-NITROPROPIONIC ACID | - |
dc.subject.keywordPlus | CYTOPLASMIC TOXICITY | - |
dc.subject.keywordPlus | NUCLEAR-LOCALIZATION | - |
dc.subject.keywordPlus | CORTICAL-NEURONS | - |
dc.subject.keywordPlus | OXIDATIVE DAMAGE | - |
dc.subject.keywordPlus | TROPHIC FACTORS | - |
dc.identifier.url | https://academic.oup.com/hmg/article/17/20/3144/593977 | - |
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