De Jesús-Cortés Héctor J, Nogueras-Ortiz Carlos J, Gearing Marla, Arnold Steven E, Vega Irving E
Department of Biology, College of Natural Sciences, University of Puerto Rico, San Juan, Puerto Rico.
Neuroreport. 2012 Nov 14;23(16):942-6. doi: 10.1097/WNR.0b013e32835982ce.
Tauopathies are a family of neurodegenerative diseases that have the pathological hallmark of intraneuronal accumulation of filaments composed of hyperphosphorylated tau proteins that tend to aggregate in an ultrastructure known as neurofibrillary tangles. The identification of mutations on the tau gene in familial cases of tauopathies underscores the pathological role of the tau protein. However, the molecular process that underlines tau-mediated neurodegeneration is not understood. Here, a proteomics approach was used to identify proteins that may be affected during the course of tau-mediated neurodegeneration in the tauopathy mouse model JNPL3. The JNPL3 mice express human tau proteins bearing a P301L mutation, which mimics the neurodegenerative process observed in humans with tauopathy. The results showed that the protein amphiphysin-1 (AMPH1) is significantly reduced in terminally ill JNPL3 mice. Specifically, the AMPH1 protein level is reduced in brain regions known to accumulate aggregates of hyperphosphorylated tau proteins. The AMPH1 protein reduction was validated in Alzheimer's disease cases. Taken together, the results suggest that the reduction of the AMPH1 protein level is a molecular event associated with the progression of tau-mediated neurodegeneration.
tau蛋白病是一类神经退行性疾病，其病理特征是神经元内由高度磷酸化的tau蛋白组成的细丝聚集，这些细丝倾向于聚集成一种称为神经原纤维缠结的超微结构。在家族性tau蛋白病病例中tau基因突变的鉴定突出了tau蛋白的病理作用。然而，tau介导的神经退行性变的分子过程尚不清楚。在此，采用蛋白质组学方法来鉴定在tau蛋白病小鼠模型JNPL3中tau介导的神经退行性变过程中可能受到影响的蛋白质。JNPL3小鼠表达携带P301L突变的人tau蛋白，该突变模拟了在患有tau蛋白病的人类中观察到的神经退行性变过程。结果显示，在晚期JNPL3小鼠中，发动蛋白-1（AMPH1）蛋白显著减少。具体而言，在已知会积累高度磷酸化tau蛋白聚集体的脑区中，AMPH1蛋白水平降低。在阿尔茨海默病病例中验证了AMPH1蛋白的减少。综上所述，结果表明AMPH1蛋白水平的降低是与tau介导的神经退行性变进展相关的分子事件。
