ICS-6, Forschungszentrum Jülich, 52425 Jülich, Germany.
Mini Rev Med Chem. 2012 May;12(5):388-98. doi: 10.2174/138955712800493942.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia. Today, only palliative therapies are available. The pathological hallmarks of AD are the presence of neurofibrillary tangles and amyloid plaques, mainly composed of the amyloid-β peptide (Aβ), in the brains of the patients. Several lines of evidence suggest that the increased production and/or decreased cleavage of Aβ and subsequent accumulation of Aβ oligomers and aggregates play a fundamental role in the disease progress. Therefore, substances which bind to Aβ and influence aggregation thereof are of great interest. A wide range of Aβ binding peptides were investigated to date for therapeutic purposes. Only very few were shown to be effective in rodent AD models or in clinical studies. Here, we review those peptides and discuss their possible mechanisms of action.
阿尔茨海默病(AD)是一种破坏性的神经退行性疾病,也是痴呆症最常见的病因。目前,仅可提供姑息疗法。AD 的病理标志物是患者大脑中存在神经原纤维缠结和淀粉样斑块,主要由淀粉样-β肽(Aβ)组成。有几条证据表明,Aβ的产生增加和/或裂解减少,以及随后 Aβ寡聚物和聚集体的积累,在疾病进展中起着根本性的作用。因此,与 Aβ结合并影响其聚集的物质具有重要意义。目前已经研究了广泛的 Aβ结合肽,以期用于治疗目的。只有极少数在啮齿动物 AD 模型或临床研究中显示出有效。在这里,我们回顾了这些肽并讨论了它们可能的作用机制。