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

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.

Inaccuracy of the HR reserve vs. V˙O2 reserve relationship during prone arm-paddling exercise in surfboard riders.

Previous studies have demonstrated that during lower-body exercise the percentage of heart rate reserve (%HRR) is equivalent to the percentage of the oxygen consumption reserve (%V˙O(2R)) but not to a percentage of the peak oxygen consumption (%V˙O(2peak)). The current study examined these relationships in trained surfboard riders (surfers) during upper-body exercise. Thirteen well-trained competitive surfers performed a stepwise, incremental, prone arm-paddling exercise test to exhaustion. For each subject, data obtained at the end of each stage (i.e., HR and V˙O(2) values) were expressed as a percentage of HRR, V˙O(2peak), and V˙O(2R) respectively and used to determine the individual %HRR-%V˙O(2peak) and %HRR-%V˙O(2R) relationships. Mean slope and intercept were calculated and compared with the line of identity (slope=1, intercept=0). The %HRR versus %V˙O(2R) regression mean slope (0.88±0.06) and intercept (20.82±4.57) were significantly different (p<0.05) from 1 and 0, respectively. Similarly, the regression of %HRR versus %V˙O(2peak) resulted in a line that differed in the slope (p<0.05) but not in the intercept (p=0.94) from the line of identity. Predicted values of %HRR were significantly higher (p<0.05) from indicated values of %V˙O(2R) for all the intensities ranging from 35% to 95% V˙O(2R). Unlike results found for lower-body exercise, a given %HRR during prone upper-body exercise was not equivalent to its corresponding %V˙O(2R). Thus, to ensure more targeted exercise intensity during arm-paddling exercise, individual HR-V˙O(2) equations should be used.