Münch G, Mayer S, Michaelis J, Hipkiss A R, Riederer P, Müller R, Neumann A, Schinzel R, Cunningham A M
Theodor-Boveri-Institute (Biocenter), Würzburg, Germany.
Biochim Biophys Acta. 1997 Feb 27;1360(1):17-29. doi: 10.1016/s0925-4439(96)00062-2.
Nucleation-dependent polymerization of beta-amyloid peptide, the major component of plaques in patients with Alzheimer's disease, is significantly accelerated by crosslinking through Advanced Glycation End-products (AGEs) in vitro. During the polymerization process, both nucleus formation and aggregate growth are accelerated by AGE-mediated crosslinking. Formation of the AGE-crosslinked amyloid peptide aggregates could be attenuated by the AGE-inhibitors Tenilsetam, aminoguanidine and carnosine. These experimental data, and clinical studies, reporting a marked improvement in cognition and memory in Alzheimer's disease patients after Tenilsetam treatment, suggest that AGEs might play an important role in the etiology or progression of the disease. Thus AGE-inhibitors may generally become a promising drug class for the treatment of Alzheimer's disease.
β-淀粉样肽的成核依赖性聚合是阿尔茨海默病患者大脑中斑块的主要成分，在体外通过晚期糖基化终产物（AGEs）交联可显著加速其聚合。在聚合过程中，AGE介导的交联加速了核的形成和聚集体的生长。AGE交联的淀粉样肽聚集体的形成可被AGE抑制剂替尼西坦、氨基胍和肌肽减弱。这些实验数据以及临床研究报告显示，替尼西坦治疗后阿尔茨海默病患者的认知和记忆有显著改善，这表明AGEs可能在该疾病的病因或进展中起重要作用。因此，AGE抑制剂可能总体上成为治疗阿尔茨海默病的一种有前景的药物类别。
