Modulation of β-amyloid and phosphorylated tau production by statin

阿尔茨海默病的疾病修饰疗法尚未建立，其最终的病理特征包括β-淀粉样蛋白(Aβ)和磷酸化的tau分别形成老年斑和神经原纤维缠结。以往的流行病学研究表明，胆固醇代谢受损与阿尔茨海默病的发生密切相关。此外，淀粉样蛋白的发生发生在富含胆固醇的膜域。他汀类药物抑制胆固醇的生物合成，并具有潜在的称为多效性的其他多种作用，是应用最广泛的降胆固醇药物。在这项研究中，我利用培养细胞研究了菌株对β-淀粉样蛋白和磷酸化tau合成的调节作用。稳定表达淀粉样前体蛋白(APP)或tau的SHSY-5Y和Neuro2a细胞最初被建立用于进一步检测。当细胞与他汀类药物孵育时，全长APP和APP C末端片段的水平升高。当他汀类药物浓度较高时，Aβ42/40比值明显升高。他汀类药物治疗对总tau水平和磷酸化tau水平无明显影响。这些结果表明，细胞通透性他汀类药物对APP代谢有影响。

Disease-modifying therapy has not been established in Alzheimer disease, in which ardinal pathological features include the accumulation of β-amyloid(Aβ) and phosphorylated tau forming senile plaque and neurofibrillary tangles, respectively. Previous epidemiological studies have suggested there is close link between impaired cholesterol metabolism and development of Alzheimer disease. Furthermore, amyloidogenesis occurs in cholesterol-rich membrane domains. Statins that inhibit cholesterol biosynthesis and have potential other multiple actions called pleiotropic effects, are the most widely used cholesterol-lowering agents. TheyIn this study, I investigated the effects of stain on modulation of β-amyloid and phosphorylated tau production using culture cells. SHSY-5Y and Neuro2a cells that stably express either amyloid precursor protein (APP) or tau were initially established for further assay. When cells were incubated with statin, the levels of full-length APP and APP C-terminal fragments were elevated. At high concentration of statin, Aβ42/40 ratio was markedly increased. Total and phosphorylated tau levels were apparently unaffected by statin treatment. These results suggest that cell-permeable statin have an effect on APP metabolism.