Vallés-Saiz Laura, Ruiz-Gabarre Daniel, García-Escudero Vega, Perry George, Avila Jesús, Hernández Félix
Centro de Biología Molecular "Severo Ochoa", CSIC/UAM, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
J Alzheimers Dis Rep. 2022 Nov 3;6(1):677-684. doi: 10.3233/ADR-220051. eCollection 2022.
An increase in tau protein is believed to be necessary for tau aggregation. However, whether this is due to increased expression of the endogenous tau promoter or protein accumulation due to proteostasis failure remains uncertain.
To analyze the expression of GFP protein under endogenous tau promoter across different ages and within different brain areas.
We have measured direct expression of gene promotor by western blot and immunofluorescence, by means of a commercial tau knock-out mice generated by integrating GFP-encoding cDNA into exon 1 of the gene. Besides, we have analyzed the gene expression in human samples.
expression is similar in the cortex, hippocampus, and cerebellum in mice and in human samples although some differences exist between dentate gyrus and CA1 hippocampal areas in mice. Besides, we have analyzed the murine gene expression during aging (at 2, 6, 12, and 18 moths) and no differences in endogenous tau promoter expression were observed.
Our results suggest that promoter activity is similar in the brain areas studied and, therefore, tau accumulation due to aging is likely due to proteostasis failure rather than occurring at the transcriptional level.
人们认为tau蛋白的增加对于tau蛋白聚集是必要的。然而，这是由于内源性tau启动子的表达增加还是由于蛋白稳态失衡导致的蛋白积累仍不确定。
分析内源性tau启动子在不同年龄和不同脑区中绿色荧光蛋白（GFP）的表达情况。
我们通过蛋白质印迹法和免疫荧光法，利用将编码GFP的cDNA整合到tau基因外显子1中产生的商业化tau基因敲除小鼠，来检测基因启动子的直接表达。此外，我们还分析了人类样本中的tau基因表达。
小鼠和人类样本中，皮质、海马体和小脑中的tau表达相似，尽管小鼠齿状回和海马体CA1区之间存在一些差异。此外，我们分析了衰老过程中（2、6、12和18个月）小鼠的tau基因表达，未观察到内源性tau启动子表达的差异。
我们的结果表明，在所研究的脑区中tau启动子活性相似，因此，衰老导致的tau积累可能是由于蛋白稳态失衡，而非发生在转录水平。
