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

• Main Authors: Manuel Menéndez-González, Huber S. Padilla-Zambrano, Cristina Tomás-Zapico, Benjamin Fernández García
• Format: Article
• Language: English
• Published: MDPI AG 2018-03-01
• Series: Brain Sciences
• Subjects: Parkinson’s disease; alpha-synuclein; cerebrospinal fluid; immunotherapy; “CSF sink” hypothesis
• Online Access: http://www.mdpi.com/2076-3425/8/4/52

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.