期刊
HUMAN MOLECULAR GENETICS
卷 9, 期 1, 页码 133-144出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/9.1.133
关键词
-
资金
- Telethon [A.096] Funding Source: Medline
Spinal and bulbar muscular atrophy (SBMA) is associated with an abnormal expansion of the (CAG)(n) repeat in the androgen receptor (AR) gene. Similar mutations have been reported in other proteins that cause neurodegenerative disorders. The GAG-coded elongated polyglutamine (polyGln) tracts induce the formation of neuronal intracellular aggregates. We have produced a model to study the effects of potentially 'neurotoxic' aggregates in SBMA using immortalized motoneuronal cells (NSC34) transfected with AR containing polyGln repeats of different sizes [(AR.Q(n = 0, 23 or 46)]. Using chimeras of AR.Q(n) and the green fluorescent protein (GFP), we have shown that aggregate formation occurs when the polyGln tract is elongated and AR is activated by androgens, In NSC34 cells co-expressing the AR with the polyGln of pathological length (AR,Q46) and the GFP we have noted the presence of several dystrophic neurites, Cell viability analyses have shown a reduced growth/survival rate in NSC34 expressing the AR,Q46, whereas testosterone treatment partially counteracted both cell death and the formation of dystrophic neurites, These observations indicate the lack of correlation between aggregate formation and cell survival, and suggest that neuronal degeneration in SBMA might be secondary to axonal/dendritic insults.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据