Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Prion. 2013 Jan-Feb;7(1):60-5. doi: 10.4161/pri.23286. Epub 2013 Jan 1.
The concept of "prion-like" has been proposed to explain the pathogenic mechanism of the principal neurodegenerative disorders associated with protein misfolding, including Alzheimer disease (AD). Other evidence relates prion protein with AD: the cellular prion protein (PrP(C)) binds β amyloid oligomers, allegedly responsible for the neurodegeneration in AD, mediating their toxic effects. We and others have confirmed the high-affinity binding between β amyloid oligomers and PrP(C), but we were not able to assess the functional consequences of this interaction using behavioral investigations and in vitro tests. This discrepancy rather than being resolved with the classic explanations, differencies in methodological aspects, has been reinforced by new data from different sources. Here we present data obtained with PrP antibody that not interfere with the neurotoxic activity of β amyloid oligomers. Since the potential role of the PrP(C) in the neuronal dysfunction induced by β amyloid oligomers is an important issue, find reasonable explanation of the inconsistent results is needed. Even more important however is the relevance of this interaction in the context of the disease, so as to develop valid therapeutic strategies.
“朊病毒样”的概念被提出，以解释与蛋白质错误折叠相关的主要神经退行性疾病的发病机制，包括阿尔茨海默病（AD）。其他证据将朊蛋白与 AD 联系起来：细胞朊蛋白（PrP(C)）与β淀粉样寡聚体结合，据称β淀粉样寡聚体负责 AD 的神经退行性变，介导其毒性作用。我们和其他人已经证实了β淀粉样寡聚体与 PrP(C)之间的高亲和力结合，但我们无法使用行为研究和体外试验来评估这种相互作用的功能后果。这种差异与其说是通过经典解释来解决的，不如说是由于方法学方面的差异，而是通过来自不同来源的新数据得到了加强。在这里，我们展示了使用 PrP 抗体获得的数据，该抗体不会干扰β淀粉样寡聚体的神经毒性活性。由于 PrP(C)在β淀粉样寡聚体诱导的神经元功能障碍中的潜在作用是一个重要问题，因此需要对不一致的结果找到合理的解释。然而，更重要的是这种相互作用在疾病背景下的相关性，以便开发有效的治疗策略。
