Maczurek Annette, Shanmugam Kirubakaran, Münch Gerald
Department of Biochemistry and Molecular Biology/Comparative Genomics Centre, James Cook University, Townsville, Australia.
Ann N Y Acad Sci. 2008 Apr;1126:147-51. doi: 10.1196/annals.1433.026.
Alzheimer's disease (AD) is the most common cause of dementia. Neuritic amyloid plaques and concomitant chronic inflammation are prominent pathological features of AD. beta-amyloid peptide (Abeta), the major component of plaques, and advanced glycation end products (AGEs), post-translational protein modifications, are key activators of plaque-associated inflammation. Abeta, AGEs, S100b, and amphoterin bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-kappaB)-regulated cytokines. RAGE-mediated inflammation caused by glial cells and subsequent changes in neuronal glucose metabolism are likely to be important contributors to neurodegeneration in AD. As long as the neuronal damage is reversible, drugs interfering with the Abeta and AGE-RAGE pathways might be interesting novel therapeutics for the treatment of AD.
阿尔茨海默病（AD）是痴呆最常见的病因。神经炎性淀粉样斑块及伴随的慢性炎症是AD突出的病理特征。斑块的主要成分β-淀粉样肽（Aβ）以及翻译后蛋白质修饰产物晚期糖基化终末产物（AGEs）是斑块相关炎症的关键激活因子。Aβ、AGEs、S100b和双调蛋白与晚期糖基化终末产物受体（RAGE）结合，RAGE通过氧化还原敏感途径将信号从RAGE传递至核因子κB（NF-κB）调控的细胞因子。由胶质细胞引起的RAGE介导的炎症以及随后神经元葡萄糖代谢的变化可能是AD神经退行性变的重要促成因素。只要神经元损伤是可逆的，干扰Aβ和AGE-RAGE途径的药物可能是治疗AD的有趣的新型疗法。
