Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, University of Barcelona, Barcelona, Spain; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain; Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain; Institute of Neuroscience, University of Barcelona, Barcelona, Spain; Department of Pathology and Experimental Therapeutics, University of Barcelona, Hospitalet de Llobregat, Spain; Senior Consultant Neuropathology, Service of Pathology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.
Prog Neurobiol. 2018 Jun-Aug;165-167:87-102. doi: 10.1016/j.pneurobio.2018.03.001. Epub 2018 Mar 9.
Several studies have indicated that certain misfolded amyloids composed of tau, β-amyloid or α-synuclein can be transferred from cell to cell, suggesting the contribution of mechanisms reminiscent of those by which infective prions spread through the brain. This process of a 'prion-like' spreading between cells is also relevant as a novel putative therapeutic target that could block the spreading of proteinaceous aggregates throughout the brain which may underlie the progressive nature of neurodegenerative diseases. The relevance of β-amyloid oligomers and cellular prion protein (PrP) binding has been a focus of interest in Alzheimer's disease (AD). At the molecular level, β-amyloid/PrP interaction takes place in two differently charged clusters of PrP. In addition to β-amyloid, participation of PrP in α-synuclein binding and brain spreading also appears to be relevant in α-synucleopathies. This review summarizes current knowledge about PrP as a putative receptor for amyloid proteins and the physiological consequences of these interactions.
已有多项研究表明，某些由 tau、β-淀粉样蛋白或 α-突触核蛋白组成的错误折叠淀粉样蛋白可以在细胞间转移，这表明存在类似于感染性朊病毒在大脑中传播的机制。这种细胞间“类朊病毒”传播的过程也可能成为一种新的潜在治疗靶点，可以阻止蛋白聚集物在大脑中的扩散，而这可能是神经退行性疾病进展的基础。β-淀粉样蛋白寡聚物和细胞朊蛋白 (PrP) 结合的相关性一直是阿尔茨海默病 (AD) 研究的重点。在分子水平上，β-淀粉样蛋白/PrP 相互作用发生在 PrP 的两个带不同电荷的簇中。除了 β-淀粉样蛋白外，PrP 参与 α-突触核蛋白的结合和在大脑中的扩散似乎也与 α-突触核蛋白病有关。这篇综述总结了目前关于 PrP 作为淀粉样蛋白的假定受体的知识，以及这些相互作用的生理后果。
