Ce Oldham, Cj Wooten, Ab Williams, S Dixon, D Lopez
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, USA.
Int J Biomed Investig. 2018 Jan-Mar;1(1). doi: 10.31531/2581-4745.1000104. Epub 2018 Mar 30.
Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of individuals. Moreover, hypothyroidism has been identified as one of the risk factors that may contribute to the development of AD. Here, we investigated whether there was a correlation among expression levels of proteins involved in the formation of AD lesions, neurite outgrowth, and thyroid hormone levels.
Cells were grown in media supplemented with different levels of 3,5,3'-triiodothyronine (T3) and then processed for neurite outgrowth and to prepare RNA samples. RNA samples were analysed using quantitative real-time PCR. Protein levels were measured using in cell-Western blotting analysis.
By using neurite outgrowth studies, it was demonstrated that T3 treatment enhanced neurite outgrowth in NS-1 cells in a time- and dose-dependent manner. Quantitative real-time PCR studies further confirmed that NS-1 cells expressed substantial levels of TRα and significantly less TRβ, either of which could be responsible for the T3-dependent effects on neurite outgrowth. Although the overall tau protein expression was not affected in response to T3 treatment, the splicing of tau exon 10 was impacted in the direction of producing more tau molecules that excluded the exon (tau 3R).
The results of this study are critical not only to understand the probable link between hypothyroidism and AD but also in providing the basis for future prevention and treatment of AD in hypothyroid patients.
阿尔茨海默病（AD）是一种影响数百万人的神经退行性疾病。此外，甲状腺功能减退已被确定为可能导致AD发生的风险因素之一。在此，我们研究了参与AD病变形成、神经突生长的蛋白质表达水平与甲状腺激素水平之间是否存在相关性。
将细胞培养在添加了不同水平3,5,3'-三碘甲状腺原氨酸（T3）的培养基中，然后进行神经突生长处理并制备RNA样本。使用定量实时PCR分析RNA样本。使用细胞内蛋白质印迹分析测量蛋白质水平。
通过神经突生长研究表明，T3处理以时间和剂量依赖性方式增强了NS-1细胞中的神经突生长。定量实时PCR研究进一步证实，NS-1细胞表达大量水平的TRα，而TRβ水平显著较低，其中任何一种都可能是T3对神经突生长依赖性作用的原因。尽管总体tau蛋白表达在T3处理后未受影响，但tau外显子10的剪接朝着产生更多排除该外显子的tau分子（tau 3R）的方向受到影响。
本研究结果不仅对于理解甲状腺功能减退与AD之间可能的联系至关重要，而且为未来甲状腺功能减退患者AD的预防和治疗提供了依据。
