Colaco C A, Ledesma M D, Harrington C R, Avila J
Quadrant Research Foundation, Trumpington, UK.
Nephrol Dial Transplant. 1996;11 Suppl 5:7-12. doi: 10.1093/ndt/11.supp5.7.
Many approaches have and are being undertaken to treat Alzheimer's disease but, as yet, no therapy is available with any established efficacy. Given the heterogeneity of the aetiological factors involved in Alzheimer's disease and the difficulties encountered in the clinical diagnosis, the lack of pharmacological success is not surprising. Furthermore, the lack of an adequate animal model of Alzheimer's disease has delayed the development of novel therapeutic strategies. At present, and with the exception of the rarer forms of familial Alzheimer's disease, the need remains to treat the symptoms rather than the causes of the disease, primarily because the pathogenesis of Alzheimer's disease is still unknown. The evidence for the role of glycation and advanced glycation end-products (AGEs) in the formation of neurofibrillary tangles and neuritic plaques, the characteristic histopathological lesions of Alzheimer's disease, is briefly reviewed. While the role of glycation in the pathogenesis of Alzheimer's disease is not yet unequivocally proven, it is the only single protein modification that would explain the formation of both the characteristic histopathological lesions first described by Alois Alzheimer in 1907. With our improved understanding of the molecular basis for the clinical symptoms of dementia, it is hoped that the aetiological causes will afford more suitable targets for therapeutic intervention. In this respect it is interesting to note that the anti-inflammatory compounds indomethacin and acetylsalicylic acid, both inhibitors of the Maillard reaction, have been reported to have therapeutic potential and the nootropic agent tenilsetam inhibits protein cross-linking by AGEs.
人们已经采用并正在采用多种方法来治疗阿尔茨海默病，但到目前为止，尚无任何已证实有效的疗法。鉴于阿尔茨海默病涉及的病因因素具有异质性，且临床诊断存在困难，药物治疗未取得成功也就不足为奇了。此外，缺乏合适的阿尔茨海默病动物模型也延缓了新型治疗策略的开发。目前，除了罕见的家族性阿尔茨海默病形式外，仍然需要治疗疾病的症状而非病因，主要是因为阿尔茨海默病的发病机制仍然未知。本文简要回顾了糖基化和晚期糖基化终产物（AGEs）在神经原纤维缠结和神经炎性斑块形成中的作用，这些是阿尔茨海默病典型的组织病理学病变。虽然糖基化在阿尔茨海默病发病机制中的作用尚未得到明确证实，但它是唯一能够解释1907年阿洛伊斯·阿尔茨海默首次描述的典型组织病理学病变形成的单一蛋白质修饰。随着我们对痴呆临床症状分子基础的深入了解，希望病因能够为治疗干预提供更合适的靶点。在这方面，值得注意的是，抗炎化合物吲哚美辛和乙酰水杨酸都是美拉德反应的抑制剂，据报道具有治疗潜力，而益智药替尼西坦可抑制AGEs引起的蛋白质交联。
