论文标题
间隙机制在参与神经退行性疾病的有毒蛋白质聚集体的动力学中的作用
The role of clearance mechanisms in the kinetics of toxic protein aggregates involved in neurodegenerative diseases
论文作者
论文摘要
大脑中的蛋白质聚集体在认知下降和与神经退行性疾病相关的结构损伤中起着核心作用。例如，在阿尔茨海默氏病中，淀粉样蛋白斑块和tau蛋白神经纤维缠结的形成遵循不同蛋白质的积累到大骨料中，通过核定和拉长等特定的机制。这些机制已在体外进行了研究，其中总蛋白质质量得到了保存。但是，在体内，清除机制可能在限制聚集体的形成中起重要作用。在这里，我们概括了蛋白质聚集的经典模型，以考虑单体的产生和蛋白质聚集体的清除。根据清除模型，我们表明可能存在一个关键的间隙值，在该清除率值中没有发生聚合。我们的结果提供了进一步的证据，以支持清除机制在神经退行性疾病的启动和进展中起着至关重要的作用的假设。因此，是可能的治疗靶点。
Protein aggregates in the brain play a central role in cognitive decline and structural damage associated with neurodegenerative diseases. For instance, in Alzheimer's disease the formation of Amyloid-beta plaques and tau proteins neurofibrillary tangles follows from the accumulation of different proteins into large aggregates through specific mechanisms such as nucleation and elongation. These mechanisms have been studied in vitro where total protein mass is conserved. However, in vivo, clearance mechanisms may play an important role in limiting the formation of aggregates. Here, we generalise classical models of protein aggregation to take into account both production of monomers and the clearance of protein aggregates. Depending on the clearance model, we show that there may be a critical clearance value above which aggregation does not take place. Our result offers further evidence in support of the hypotheses that clearance mechanisms play a potentially crucial role in neurodegenerative disease initiation and progression; and as such, are a possible therapeutic target.
