Institute of Neurology, Medical University of Vienna, AKH 4 J, Währinger Gürtel 18-20, 1097, Vienna, Austria.
Neuromolecular Med. 2014 Jun;16(2):405-14. doi: 10.1007/s12017-014-8288-8. Epub 2014 Jan 25.
Aging is one of the major risk factors for Alzheimer's disease (AD). Sirtuins are associated with prolonged life span. To examine whether the expression levels of sirtuins associate with the progression of AD or not, we performed a comparative immunoblotting and immunohistochemical study of SIRT1, 3, and 5 in the entorhinal cortex and hippocampal subregions and white matter in 45 cases grouped according to Braak and Braak stages of neurofibrillary degeneration. In addition, we compared the expression levels with the local load of tau and amyloid-beta deposits, evaluated using morphometry. Our study revealed that (1) the neuronal subcellular redistribution of SIRT1 parallels the decrease in its expression, suggesting stepwise loss of neuroprotection dependent on the neuronal population; (2) in contrast to SIRT1 and 3, expression of SIRT5 increases during the progression of AD; (3) which might be related to its appearance in activated microglial cells. The complex patterns of the expression of sirtuins in relation to tissue damage should be taken into account when searching for therapies interacting with sirtuins.
衰老是阿尔茨海默病（AD）的主要危险因素之一。沉默调节蛋白与寿命延长有关。为了研究沉默调节蛋白的表达水平是否与 AD 的进展有关，我们对 45 例根据神经纤维变性的 Braak 和 Braak 阶段分组的病例的海马回和海马亚区以及白质中的 SIRT1、3 和 5 进行了比较免疫印迹和免疫组织化学研究。此外，我们使用形态计量学比较了表达水平与tau 和淀粉样β沉积的局部负荷。我们的研究表明：（1）SIRT1 的神经元亚细胞重新分布与表达水平的降低相平行，表明依赖于神经元群体的神经保护逐渐丧失；（2）与 SIRT1 和 3 相反，SIRT5 的表达在 AD 的进展过程中增加；（3）这可能与其在激活的小胶质细胞中的出现有关。在寻找与沉默调节蛋白相互作用的治疗方法时，应该考虑到沉默调节蛋白表达与组织损伤之间的复杂关系。
