Vignini Arianna, Giulietti Alessia, Nanetti Laura, Raffaelli Francesca, Giusti Lucia, Mazzanti Laura, Provinciali Leandro
Department of Clinical Science, Section of Biochemistry, Universita Politecnica delle Marche, Via Tronto 10 A, 60020 Ancona, Italy.
Curr Diabetes Rev. 2013 May;9(3):218-27. doi: 10.2174/1573399811309030003.
Several research groups have begun to associate the Alzheimer Disease (AD) to Diabetes Mellitus (DM), obesity and cardiovascular disease. This relationship is so close that some authors have defined Alzheimer Disease as Type 3 Diabetes. Numerous studies have shown that people with type 2 diabetes have twice the incidence of sporadic AD. Insulin deficiency or insulin resistance facilitates cerebral β-amyloidogenesis in murine model of AD, accompanied by a significant elevation in APP (Amyloid Precursor Protein) and BACE1 (β-site APP Cleaving Enzime 1). Similarly, deposits of Aβ produce a loss of neuronal surface insulin receptors and directly interfere with the insulin signaling pathway. Furthermore, as it is well known, these disorders are both associated to an increased cardiovascular risk and an altered cholesterol metabolism, so we have analyzed several therapies which recently have been suggested as a remedy to treat together AD and DM. The aim of the present review is to better understand the strengths and drawbacks of these therapies.
几个研究小组已开始将阿尔茨海默病(AD)与糖尿病(DM)、肥胖症和心血管疾病联系起来。这种关系非常密切,以至于一些作者将阿尔茨海默病定义为3型糖尿病。大量研究表明,2型糖尿病患者患散发性AD的几率是正常人的两倍。在AD小鼠模型中,胰岛素缺乏或胰岛素抵抗会促进大脑β-淀粉样蛋白生成,同时淀粉样前体蛋白(APP)和β-分泌酶1(BACE1)显著升高。同样,β-淀粉样蛋白(Aβ)沉积会导致神经元表面胰岛素受体丧失,并直接干扰胰岛素信号通路。此外,众所周知,这些疾病都与心血管风险增加和胆固醇代谢改变有关,因此我们分析了几种最近被建议用于同时治疗AD和DM的疗法。本综述的目的是更好地了解这些疗法的优缺点。