Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, U.P., India.
Mol Neurobiol. 2016 Jan;53(1):109-119. doi: 10.1007/s12035-014-8988-y. Epub 2014 Nov 19.
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-β (TGF-β) 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-β pathway, have a role to play in modulating the disease outcome. Employing transgenic C. elegans model, we studied β-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-β-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.
转录因子及其激活的相关信号分子在各种生物学过程中发挥着重要作用，这一点已经得到了充分的阐明。其中一个重要的转录因子是转化生长因子-β（TGF-β）途径，它在神经元细胞存活中起着深远的作用——这一过程在多种情况下都会出现异常，包括各种神经疾病。阿尔茨海默病（AD）就是其中一种情况，其中错误折叠的蛋白质有毒积累，细胞信号受到干扰，神经元细胞死亡。我们试图研究与 TGF-β途径相关的转录共因子是否在调节疾病结果中发挥作用。我们使用转基因秀丽隐杆线虫模型研究了β-淀粉样蛋白聚集、乙酰胆碱水平和相关终点，并发现 SMAD 转录共因子 Sma-9 可以调节 AD 相关的结果。我们的研究得出结论，Sma-9 是 TGF-β 介导的信号通路的一个子集，它可以作为神经退行性 AD 的一个潜在靶点，因为它可以影响神经元和机体的存活，并在限制 AD 的不利影响方面发挥关键作用。
