Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease
Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease
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DOI：
10.1196/annals.1433.026
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Muench, Gerald
中科院分区：
文献类型：
--
作者：
Maczurek, Annette;Shanmugam, Kirubakaran;Muench, Gerald
阿尔茨海默病（AD）是痴呆症最常见的原因。神经炎性淀粉样斑块和伴随的慢性炎症是AD的突出病理特征。β-淀粉样肽（A β），斑块的主要成分，和晚期糖基化终产物（AGEs），翻译后蛋白质修饰，是斑块相关炎症的关键活化剂。A β、AGEs、S100 B和AGE结合AGEs受体（AGE），后者通过氧化还原敏感途径将信号从AGE传递到核因子κ-B（NF-κ B）调节的细胞因子。由神经胶质细胞引起的RAGE介导的炎症和随后神经元葡萄糖代谢的变化可能是AD神经变性的重要贡献者。只要神经元损伤是可逆的，干扰A β和AGE-β通路的药物可能是治疗AD的有趣的新疗法。
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 (A beta), the major component of plaques, and advanced glycation end products (AGEs), post-translational protein modifications, are key activators of plaque-associated inflammation. A beta, 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-kappa B)-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 A beta and AGE-RAGE pathways might be interesting novel therapeutics for the treatment of AD.