Alvarez Javier, Alvarez-Illera Pilar, Santo-Domingo Jaime, Fonteriz Rosalba I, Montero Mayte
Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Unidad de Excelencia Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and CSIC, Ramón y Cajal, 7, E-47005 Valladolid, Spain.
Biomedicines. 2022 Jan 26;10(2):288. doi: 10.3390/biomedicines10020288.
Alzheimer's disease (AD) is the most frequent cause of dementia. After decades of research, we know the importance of the accumulation of protein aggregates such as β-amyloid peptide and phosphorylated tau. We also know that mutations in certain proteins generate early-onset Alzheimer's disease (EOAD), and many other genes modulate the disease in its sporadic form. However, the precise molecular mechanisms underlying AD pathology are still unclear. Because of ethical limitations, we need to use animal models to investigate these processes. The nematode has received considerable attention in the last 25 years, since the first AD models overexpressing Aβ peptide were described. We review here the main results obtained using this model to study AD. We include works studying the basic molecular mechanisms of the disease, as well as those searching for new therapeutic targets. Although this model also has important limitations, the ability of this nematode to generate knock-out or overexpression models of any gene, single or combined, and to carry out toxicity, recovery or survival studies in short timeframes with many individuals and at low cost is difficult to overcome. We can predict that its use as a model for various diseases will certainly continue to increase.
阿尔茨海默病(AD)是痴呆最常见的病因。经过数十年研究,我们了解到蛋白质聚集体如β-淀粉样肽和磷酸化tau蛋白积累的重要性。我们也知道某些蛋白质的突变会引发早发性阿尔茨海默病(EOAD),还有许多其他基因在散发性形式的疾病中起调节作用。然而,AD病理背后的确切分子机制仍不清楚。由于伦理限制,我们需要使用动物模型来研究这些过程。在过去25年里,自首个过表达Aβ肽的AD模型被描述以来,线虫受到了相当多的关注。我们在此回顾使用该模型研究AD所获得的主要结果。我们纳入了研究该疾病基本分子机制的工作,以及那些寻找新治疗靶点的工作。尽管这个模型也有重要局限性,但这种线虫能够生成任何单个或组合基因的敲除或过表达模型,并能在短时间内对许多个体进行低成本的毒性、恢复或存活研究,这一点很难被超越。我们可以预测,它作为各种疾病模型的应用肯定会继续增加。