Gasparini Laura, Netzer William J, Greengard Paul, Xu Huaxi
Nicox Research Institute, Via Ariosto 21, 20091 Bresso, Milan, Italy.
Trends Pharmacol Sci. 2002 Jun;23(6):288-93. doi: 10.1016/s0165-6147(02)02037-0.
Age-related changes in hormone levels are determinants of a variety of human diseases. Insulin is known to affect numerous brain functions including cognition and memory, and several clinical studies have established links between Alzheimer's disease (AD), insulin resistance and diabetes mellitus. These are reinforced by biological studies that reveal the effects of insulin on the molecular and cellular mechanisms that underlie the pathology of AD. For example, insulin regulates phosphorylation of tau protein, which underlies neurofibrillary lesions in the brains of AD patients. Insulin also affects the metabolism of beta-amyloid, the main constituent of AD amyloid pathology. Here, we discuss clinical and biological data that highlight potential targets for therapeutic intervention.
激素水平的年龄相关变化是多种人类疾病的决定因素。已知胰岛素会影响包括认知和记忆在内的多种脑功能，并且多项临床研究已确立了阿尔茨海默病（AD）、胰岛素抵抗和糖尿病之间的联系。揭示胰岛素对AD病理学基础的分子和细胞机制影响的生物学研究进一步强化了这些联系。例如，胰岛素调节tau蛋白的磷酸化，而tau蛋白磷酸化是AD患者大脑神经原纤维病变的基础。胰岛素还会影响β-淀粉样蛋白的代谢，β-淀粉样蛋白是AD淀粉样病变的主要成分。在此，我们讨论突出治疗干预潜在靶点的临床和生物学数据。
