Pearson Hugh A, Peers Chris
Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
J Physiol. 2006 Aug 15;575(Pt 1):5-10. doi: 10.1113/jphysiol.2006.111203. Epub 2006 Jun 29.
Alzheimer's disease is recognized post mortem by the presence of extracellular senile plaques, made primarily of aggregation of amyloid beta peptide (Abeta). This peptide has consequently been regarded as the principal toxic factor in the neurodegeneration of Alzheimer's disease. As such, intense research effort has been directed at determining its source, activity and fate, primarily with a view to preventing its formation or its biological activity, or promoting its degradation. Clearly, much progress has been made concerning its formation by proteolytic processing of the amyloid precursor protein, and its degradation by enzymes such as neprilysin and insulin degrading enzyme. The activities of Abeta, however, are numerous and yet to be fully elucidated. What is currently emerging from such studies is a diffuse but steadily growing body of data that suggests Abeta has important physiological functions and, further, that it should only be regarded as toxic when its production and degradation are imbalanced. Here, we review these data and suggest that physiological levels of Abeta have important physiological roles, and may even be crucial for neuronal cell survival. Thus, the view of Abeta being a purely toxic peptide requires re-evaluation.
阿尔茨海默病在尸检时通过细胞外老年斑的存在得以确认，这些老年斑主要由β淀粉样肽（Aβ）聚集而成。因此，这种肽被认为是阿尔茨海默病神经退行性变的主要毒性因子。正因如此，大量的研究工作致力于确定其来源、活性和去向，主要目的是防止其形成或抑制其生物活性，或促进其降解。显然，在通过淀粉样前体蛋白的蛋白水解加工形成Aβ以及通过诸如中性内肽酶和胰岛素降解酶等酶对其进行降解方面已经取得了很大进展。然而，Aβ的活性多种多样，尚未完全阐明。目前从这些研究中逐渐浮现出的是一系列分散但不断增加的数据，这些数据表明Aβ具有重要的生理功能，而且进一步表明，只有当其产生和降解失衡时才应被视为有毒。在此，我们回顾这些数据，并表明生理水平的Aβ具有重要的生理作用，甚至可能对神经元细胞存活至关重要。因此，认为Aβ是一种纯粹有毒肽的观点需要重新评估。
