SMAD Transcription Factor, Sma-9, Attunes TGF-β Signaling Cascade Towards Modulating Amyloid Beta Aggregation and Associated Outcome in Transgenic C-elegans
SMAD Transcription Factor, Sma-9, Attunes TGF-β Signaling Cascade Towards Modulating Amyloid Beta Aggregation and Associated Outcome in Transgenic C-elegans
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DOI：
10.1007/s12035-014-8988-y
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发表时间：
2016-01-01
影响因子：
5.1
通讯作者：
Nazir, Aamir
中科院分区：
文献类型：
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作者：
Haque, Rizwanul;Nazir, Aamir
转录因子以及激活它们的相关信号分子在各种生物过程中的重要作用已得到充分解读。其中一个重要的转录因子，即转化生长因子 -β（TGF -β）通路，在神经元细胞存活中具有深远的作用——在包括多种神经系统疾病在内的多种情况下，这一过程会出现异常。阿尔茨海默病（AD）就是这样一种疾病，其中错误折叠的蛋白质有毒性积累，细胞信号传导被破坏，进而导致神经元细胞死亡。我们努力研究与TGF -β通路相关的转录辅因子是否在调节疾病结果方面发挥作用。利用转基因秀丽隐杆线虫模型，我们研究了β - 淀粉样蛋白聚集、乙酰胆碱水平以及相关指标，并发现SMAD转录辅因子Sma - 9调节与AD相关的结果。我们的研究得出结论，Sma - 9作为TGF -β介导的信号通路的一部分，可能是神经退行性阿尔茨海默病的一个潜在靶点，因为它可以影响神经元以及生物体的存活，并在限制AD的不良影响方面发挥关键作用。
The considerable roles of transcription factors, and the associated signaling molecules that activate them, are well deciphered in the context of various biological processes. One of the important transcription factors, the transforming growth factor-beta (TGF-beta) pathway, has a profound role in neuronal cell survival-a process that gets awry in multiple conditions which include various neurological ailments. Alzheimer's disease (AD) is one such condition wherein toxic buildup of misfolded proteins occurs, cellular signaling gets disrupted, and neuronal cell death ensues. We endeavored to study whether the transcriptional cofactors, associated with the TGF-beta pathway, have a role to play in modulating the disease outcome. Employing transgenic C. elegans model, we studied beta-amyloid aggregation, acetylcholine levels, and associated endpoints and figured that SMAD transcriptional cofactor, Sma-9, modulates the outcome associated with AD. Our studies conclude that Sma-9, a subset of the TGF-beta-mediated signaling pathway, can be a potential target in neurodegenerative AD as it can influence neuronal, and organismal, survival and play crucial role in limiting adverse effects of AD.