Menéndez-González Manuel, Padilla-Zambrano Huber S, Tomás-Zapico Cristina, García Benjamin Fernández
Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo 33011, Spain.
Department of Morphology and Cell Biology, University of Oviedo, Oviedo 33006, Spain.
Brain Sci. 2018 Mar 23;8(4):52. doi: 10.3390/brainsci8040052.
This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson's disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain.
这篇概念文章旨在阐述将脑脊液（CSF）中的细胞外α-突触核蛋白（α-Syn）作为从帕金森病（PD）大脑中清除该蛋白的新策略的基本原理。α-突触核蛋白错误折叠并在细胞内聚集成路易小体被认为在PD发病机制中起关键作用。最近的研究表明，少量的单体和寡聚α-突触核蛋白通过胞吐作用从神经元细胞释放出来，并且这种细胞外α-突触核蛋白会导致神经退行性变、α-突触核蛋白病理的进行性传播和神经炎症。在PD中，细胞外寡聚α-突触核蛋白在细胞间液（ISF）和脑脊液之间不断地处于平衡状态。因此，我们预计持续清除脑脊液中的寡聚α-突触核蛋白将使ISF中的该蛋白稳定清除，防止其在大脑中的传播和沉积。
