Nieznanski Krzysztof, Surewicz Krystyna, Chen Shugui, Nieznanska Hanna, Surewicz Witold K
Department of Physiology and Biophysics, Case Western Reserve University , Cleveland, Ohio 44106, United States.
ACS Chem Neurosci. 2014 May 21;5(5):340-5. doi: 10.1021/cn500019c. Epub 2014 Apr 1.
Recent studies indicate that the pathogenesis of Alzheimer disease may be related to the interaction between prion protein (PrP) and certain oligomeric species of Aβ peptide. However, the mechanism of this interaction remains unclear and controversial. Here we provide direct experimental evidence that, in addition to previously demonstrated binding to Aβ oligomers, PrP also interacts with mature Aβ fibrils. However, contrary to the recent claim that PrP causes fragmentation of Aβ fibrils into oligomeric species, no evidence for such a disassembly could be detected in the present study. In contrast, our data indicate that the addition of PrP to preformed Aβ fibrils results in a lateral association of individual fibrils into larger bundles. These findings have potentially important implications for understanding the mechanism by which PrP might impact Aβ toxicity as well as for the emerging efforts to use PrP-derived compounds as inhibitors of Aβ-induced neurodegeneration.
最近的研究表明，阿尔茨海默病的发病机制可能与朊病毒蛋白（PrP）和某些Aβ肽寡聚体之间的相互作用有关。然而，这种相互作用的机制仍不清楚且存在争议。在此，我们提供了直接的实验证据，即除了先前证明的与Aβ寡聚体结合外，PrP还与成熟的Aβ纤维相互作用。然而，与最近声称PrP导致Aβ纤维断裂成寡聚体的说法相反，在本研究中未检测到这种拆解的证据。相反，我们的数据表明，将PrP添加到预先形成的Aβ纤维中会导致单个纤维横向结合成更大的束。这些发现对于理解PrP可能影响Aβ毒性的机制以及将PrP衍生化合物用作Aβ诱导神经退行性变抑制剂的新努力具有潜在的重要意义。
