Duran-Aniotz Claudia, Morales Rodrigo, Moreno-Gonzalez Ines, Hu Ping Ping, Fedynyshyn Joseph, Soto Claudio
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America ; Universidad de los Andes, Facultad de Medicina, Santiago, Chile.
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas, United States of America.
PLoS One. 2014 Feb 12;9(2):e89014. doi: 10.1371/journal.pone.0089014. eCollection 2014.
Recent studies in animal models of Alzheimer's disease (AD) show that amyloid-beta (Aβ) misfolding can be transmissible; however, the mechanisms by which this process occurs have not been fully explored. The goal of this study was to analyze whether depletion of aggregates from an AD brain suppresses its in vivo "seeding" capability. Removal of aggregates was performed by using the Aggregate Specific Reagent 1 (ASR1) compound which has been previously described to specifically bind misfolded species. Our results show that pre-treatment with ASR1-coupled magnetic beads reduces the in vivo misfolding inducing capability of an AD brain extract. These findings shed light respect to the active principle responsible for the prion-like spreading of Alzheimer's amyloid pathology and open the possibility of using seeds-capturing reagents as a promising target for AD treatment.
最近在阿尔茨海默病（AD）动物模型中的研究表明，β-淀粉样蛋白（Aβ）错误折叠具有传染性；然而，这一过程发生的机制尚未得到充分探索。本研究的目的是分析从AD大脑中清除聚集体是否会抑制其体内“播种”能力。通过使用先前已描述的特异性结合错误折叠物种的聚集特异性试剂1（ASR1）化合物来清除聚集体。我们的结果表明，用ASR1偶联磁珠进行预处理可降低AD脑提取物在体内诱导错误折叠的能力。这些发现揭示了导致阿尔茨海默病淀粉样病理的朊病毒样传播的活性成分，并为将种子捕获试剂作为AD治疗的有前景靶点开辟了可能性。
