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Inhibition of Transglutaminases protects against 3-nitroprionic acid toxicity in mutant huntingtin expressing cellsстатья Краткое сообщение
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 3 июля 2019 г.
- Авторы: McConoughey SJ, Chavez JC, Krasnikov BF
- Журнал: Journal of Neurochemistry
- Том: 102
- Год издания: 2007
- Издательство: Blackwell Publishing Inc.
- Местоположение издательства: United Kingdom
- Первая страница: 165
- Последняя страница: 166
- Аннотация: Increased expression of nuclear-encoded mitochondrial pro-teins (such as cytochromec) will enhance mitochondrialbiogenesis/respiration which we hypothesis will increasesurvival of mutant huntingtin (mhtt) encoding neurons. Workin Huntington Disease (HD) has long implicated energeticstress as a major cause of pathology. Numerous mitochondrialcomplexes have been reported to be impaired within HDpatients as well as HD model mice. We hypothesize thisinability to cope with metabolic stress is due to the excessiveactivity of transglutaminase 2 (TG2) that has been reported inHD patients and models alike.We have found that inhibition of TG2 mediated crosslinkinghas several pro-survival effects within mhtt-expressing cellsthat appear to be due to a de-repression of nuclear-encodedmitochondrial genes. The basal level of cytcpromoter activitywas found to be lower in the mhtt-expressing cells than that ofhtt cells. Also, this promoter is activated upon treatment ofTG2 inhibitors. This work is furthered by the observation thatcytcand PGC-1aRNA and protein levels are increased uponTG2 inhibition. Furthermore, TG2 inhibitors are also protec-tive against 3-NP toxicity in a cells expressing mhtt as well asrat primary cortical neurons. While there is still work to bedone to solidify this connection between inhibition of TG2,increased expression of nuclear-encoded mitochondrial pro-teins, and increased survival of mhtt expressing cells data thusfar supports our global hypothesis that inhibiting TG2 cross-linking will ultimately result in increased survival of mhttexpressing cells.
- Добавил в систему: Красников Борис Фёдорович