Sun Miao-Kun, Alkon Daniel L
Blanchette Rockefeller Neurosciences Institute, Academic & Research Building, Rockville, Maryland 20850, USA.
Drugs Today (Barc). 2006 Jul;42(7):481-9. doi: 10.1358/dot.2006.42.7.973588.
The existence of links between Alzheimer's disease and diabetes is an important topic currently under active debate. Establishing such links if they exist and defining their common pathogenesis and pathophysiological mechanisms may lead to new concepts and research directions for the pharmacological treatment of Alzheimer's disease and diabetes. Alzheimer's disease is associated with peripheral and central insulin abnormalities. Cognitive capacities are often impaired in patients with diabetes. There are many mechanisms by which insulin-signaling abnormalities may affect clinical and pathological outcome of Alzheimer's disease. Insulin resistance and dysregulation of the degradation of neurotoxic amyloid and insulin appear at the core of the links between Alzheimer's disease and diabetes. Functions and expression of insulysin, an enzyme involved in the degradation of neurotoxic amyloid peptides and insulin, are usually impaired or reduced in Alzheimer's disease and diabetes. The increased occurrence of insulin resistance in Alzheimer's disease suggests that improving insulin effectiveness and insulysin activity may have therapeutic value in Alzheimer's disease patients and therefore is worth intensive investigation.
阿尔茨海默病与糖尿病之间联系的存在是当前正在积极讨论的一个重要话题。如果存在这样的联系并确定其共同的发病机制和病理生理机制,可能会为阿尔茨海默病和糖尿病的药物治疗带来新的概念和研究方向。阿尔茨海默病与外周和中枢胰岛素异常有关。糖尿病患者的认知能力常常受损。胰岛素信号异常可能通过多种机制影响阿尔茨海默病的临床和病理结果。胰岛素抵抗以及神经毒性淀粉样蛋白和胰岛素降解的失调似乎是阿尔茨海默病与糖尿病之间联系的核心。胰岛素降解酶(一种参与神经毒性淀粉样肽和胰岛素降解的酶)的功能和表达在阿尔茨海默病和糖尿病中通常受损或降低。阿尔茨海默病中胰岛素抵抗发生率的增加表明,提高胰岛素有效性和胰岛素降解酶活性可能对阿尔茨海默病患者具有治疗价值,因此值得深入研究。