DC Field | Value | Language |
---|---|---|
dc.contributor.author | Grosso, Hilary | ko |
dc.contributor.author | Woo, Jong-Min | ko |
dc.contributor.author | Lee, Kang-Woo | ko |
dc.contributor.author | Im, Joo-Young | ko |
dc.contributor.author | Masliah, Eliezer | ko |
dc.contributor.author | Junn, Eunsung | ko |
dc.contributor.author | Mouradian, M. Maral | ko |
dc.date.accessioned | 2016-04-06T09:44:08Z | - |
dc.date.available | 2016-04-06T09:44:08Z | - |
dc.date.created | 2015-06-12 | - |
dc.date.created | 2015-06-12 | - |
dc.date.created | 2015-06-12 | - |
dc.date.issued | 2014-10 | - |
dc.identifier.citation | FASEB JOURNAL, v.28, no.10, pp.4280 - 4291 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/10203/202980 | - |
dc.description.abstract | alpha-Synuclein is a key pathogenic protein that aggregates in hallmark lesions in Parkinson's disease and other alpha-synucleinopathies. Prior in vitro studies demonstrated that it is a substrate for cross-linking by transglutaminase 2 (TG2) into higher-order species. Here we investigated whether this increased aggregation occurs in vivo and whether TG2 exacerbates alpha-synuclein toxicity in Mus musculus and Saccharomyces cerevisiae. Compared with alpha-synuclein transgenic (Syn(Tg)) mice, animals double transgenic for human alpha-synuclein and TG2 (TG2(Tg)/Syn(Tg)) manifested greater high-molecular-weight insoluble species of alpha-synuclein in brain lysates and developed alpha-synuclein aggregates in the synaptic vesicle fraction. In addition, larger proteinase K-resistant aggregates developed, along with increased thioflavin-S-positive amyloid fibrils. This correlated with an exaggerated neuroinflammatory response, as seen with more astrocytes and microglia. Further neuronal damage was suggested by greater morphological disruption of nerve fibers and a trend toward decreased c-Fos immunoreactive neurons. Finally, the performance of TG2(Tg)/Syn(Tg) animals on motor behavioral tasks was worse relative to Syn(Tg) mice. Greater toxicity of alpha-synuclein was also demonstrated in yeast cells coexpressing TG2. Our findings demonstrate that TG2 promotes the aggregation of alpha-synuclein in vivo and that this is associated with aggravated toxicity of alpha-synuclein and its downstream neuropathologic consequences. | - |
dc.language | English | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.subject | NEURONAL CELL-DEATH | - |
dc.subject | PARKINSONS-DISEASE | - |
dc.subject | TISSUE TRANSGLUTAMINASE | - |
dc.subject | MOUSE MODEL | - |
dc.subject | MEMBRANE INTERACTIONS | - |
dc.subject | HUNTINGTONS-DISEASE | - |
dc.subject | CROSS-LINKING | - |
dc.subject | INHIBITION | - |
dc.subject | BRAIN | - |
dc.subject | NEURODEGENERATION | - |
dc.title | Transglutaminase 2 exacerbates alpha-synuclein toxicity in mice and yeast | - |
dc.type | Article | - |
dc.identifier.wosid | 000342222700008 | - |
dc.identifier.scopusid | 2-s2.0-84907699043 | - |
dc.type.rims | ART | - |
dc.citation.volume | 28 | - |
dc.citation.issue | 10 | - |
dc.citation.beginningpage | 4280 | - |
dc.citation.endingpage | 4291 | - |
dc.citation.publicationname | FASEB JOURNAL | - |
dc.identifier.doi | 10.1096/fj.14-251413 | - |
dc.contributor.nonIdAuthor | Grosso, Hilary | - |
dc.contributor.nonIdAuthor | Woo, Jong-Min | - |
dc.contributor.nonIdAuthor | Im, Joo-Young | - |
dc.contributor.nonIdAuthor | Masliah, Eliezer | - |
dc.contributor.nonIdAuthor | Junn, Eunsung | - |
dc.contributor.nonIdAuthor | Mouradian, M. Maral | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Parkinson&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | protein misfolding | - |
dc.subject.keywordAuthor | neurodegeneration | - |
dc.subject.keywordPlus | NEURONAL CELL-DEATH | - |
dc.subject.keywordPlus | PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | TISSUE TRANSGLUTAMINASE | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | MEMBRANE INTERACTIONS | - |
dc.subject.keywordPlus | HUNTINGTONS-DISEASE | - |
dc.subject.keywordPlus | CROSS-LINKING | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | NEURODEGENERATION | - |
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