期刊
ACTA NEUROPATHOLOGICA
卷 113, 期 5, 页码 543-548出版社
SPRINGER
DOI: 10.1007/s00401-007-0221-x
关键词
TDP-43; hnRNP; SMN; ubiquitin; FTD
资金
- NIA NIH HHS [AG17586, AG10124] Funding Source: Medline
TDP-43 was recently identified as the major disease protein in neuronal inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). TDP-43 becomes redistributed from the nucleus to the cytoplasm, ubiquitinated, hyperphosphorylated and cleaved to generate C-terminal fragments, thereby linking mismetabolism of TDP-43 to the pathogenesis of FTLD-U. The function of TDP-43 is unclear, however it has been shown that TDP-43 might act as transcription repressor and activator of exon skipping through interaction with proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) family as well as a scaffold for nuclear bodies through interactions with survival motor neuron protein. To investigate whether these binding partners might be associated with TDP-43 pathology, we studied the expression and localization of proteins of the hnRNP family (hnRNP A1, A2/B1, C1/C2) and SMN protein in affected brain regions in patients with sporadic and familial FTLD-U and normal control brains by immunohistochemistry and biochemical analysis. In contrast to TDP-43, no changes in subcellular distribution, no labeling of pathologic inclusions and no biochemical alterations were detectable for the tested hnRNPs and SMN in FTLD-U brains compared to controls. These results argue against a role of these binding partners in the pathogenesis of FTLD-U and emphasize the specificity of TDP-43 as marker for FTLD-U pathology.
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