Institute of Cytology Russian Academy of Science, St. Petersburg, Tikhoretsky ave. 4, 194064, Russia.
Institute of Cytology Russian Academy of Science, St. Petersburg, Tikhoretsky ave. 4, 194064, Russia; Peter the Great St.-Petersburg Polytechnic University, St. Petersburg, Polytechnicheskaya 29, 195251, Russia.
Int J Biol Macromol. 2020 May 1;150:681-694. doi: 10.1016/j.ijbiomac.2020.01.290. Epub 2020 Feb 11.
Accumulation of amyloid fibrils in organism accompanies many serious diseases, such as Alzheimer's and Parkinson's diseases, diabetes, prion diseases, etc. It is generally accepted that amyloids are highly resistant to degradation, which complicates their elimination in vivo and is one of the reasons for their pathogenicity. However, using a wide range of physicochemical approaches and specially elaborated method for the tested samples preparation by equilibrium microdialysis technique, it is proved that the stability of amyloids is greatly exaggerated. It turned out that amyloid fibrils formed from at least two amyloidogenic proteins, one of which is a model object for fibrils studying and the second is the cause of hemodialysis amyloidosis in an acute renal failure, are less stable than monomeric proteins. A mechanism of the degradation/reassembly of amyloid fibrils was proposed. It was shown that amyloid «seed» is a factor affecting not only the rate of the fibrils formation, but also their structure. Obtained results are a step towards identifying effects that can lead to degradation of amyloids and their clearance without adverse influence on the functionally active state of the protein or to change the structure and, as a result, the pathogenicity of these protein aggregates.
淀粉样纤维在生物体中的积累伴随着许多严重的疾病，如阿尔茨海默病、帕金森病、糖尿病、朊病毒病等。人们普遍认为淀粉样纤维具有很强的抗降解性，这使得它们在体内的清除变得复杂，也是它们致病的原因之一。然而，通过广泛的物理化学方法和专门设计的平衡微透析技术测试样品制备方法，证明淀粉样纤维的稳定性被大大夸大了。事实证明，由至少两种淀粉样蛋白形成的淀粉样纤维，其中一种是纤维研究的模型对象，另一种是急性肾功能衰竭中血液透析淀粉样变性的原因，其稳定性不如单体蛋白。提出了淀粉样纤维降解/重组的机制。结果表明，淀粉样“种子”不仅是影响纤维形成速度的因素，也是影响其结构的因素。这些结果是朝着鉴定可以导致淀粉样纤维降解和清除的作用迈出的一步，而不会对蛋白质的功能活性状态产生不利影响，也不会改变这些蛋白质聚集体的结构，从而改变它们的致病性。
