α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects

• Published in: Molecular neurobiology Vol. 55; no. 3; pp. 2653 - 2675
• Main Authors: Daniele, Simona, Pietrobono, Deborah, Fusi, Jonathan, Iofrida, Caterina, Chico, Lucia, Petrozzi, Lucia, Gerfo, Annalisa Lo, Baldacci, Filippo, Galetta, Fabio, Siciliano, Gabriele, Bonuccelli, Ubaldo, Santoro, Gino, Trincavelli, Maria Letizia, Franzoni, Ferdinando, Martini, Claudia
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2018; Springer Nature B.V
• Subjects: Adult; Aged; Aging; alpha-Synuclein - blood; Alzheimer's disease; Amyloid beta-Peptides - blood; Antioxidants; Antioxidants - metabolism; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cohort Studies; Erythrocytes; Erythrocytes - metabolism; Exercise; Exercise - physiology; Female; Free radicals; Geriatrics; Healthy Volunteers; Humans; Hydroxyl radicals; Male; Middle Aged; Neurobiology; Neurodegenerative diseases; Neurology; Neurosciences; Oxidative stress; Oxidative Stress - physiology; Peptide Fragments - blood; Physical activity; Physical Endurance - physiology; Physical fitness; Physical training; Protein Aggregates - physiology; Protein folding; Proteins; Synuclein; Tau protein; tau Proteins - blood; Young Adult; β-Amyloid; Physical exercise; α-Synuclein; Antioxidant capability; Protein misfolding; Neurodegenerative diseases; β-Amyloid; Tau; α-Synuclein heterocomplexes
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-017-0523-5

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid 1–42 (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aβ, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aβ accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aβ or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aβ aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding.