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Brain Sci. 2018, 8(4), 52; https://doi.org/10.3390/brainsci8040052

Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease

1
Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
2
Department of Morphology and Cell Biology, University of Oviedo, Oviedo 33006, Spain
3
Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo 33006, Spain
4
Estudiante de Medicina. Centro de Investigaciones Biomédicas (CIB), Faculty of medicine, University of Cartagena, Cartagena 130001, Colombia
5
Department of Functional Biology, University of Oviedo, Oviedo 33006, Spain
*
Author to whom correspondence should be addressed.
Received: 24 February 2018 / Revised: 17 March 2018 / Accepted: 22 March 2018 / Published: 23 March 2018
(This article belongs to the Special Issue Pathogenesis and Treatment of Neurodegenerative Diseases)
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Abstract

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. View Full-Text
Keywords: Parkinson’s disease; alpha-synuclein; cerebrospinal fluid; immunotherapy; “CSF sink” hypothesis Parkinson’s disease; alpha-synuclein; cerebrospinal fluid; immunotherapy; “CSF sink” hypothesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Menéndez-González, M.; Padilla-Zambrano, H.S.; Tomás-Zapico, C.; García, B.F. Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease. Brain Sci. 2018, 8, 52.

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