α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects
α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects
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DOI：
10.1007/s12035-017-0523-5
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发表时间：
2018-03-01
影响因子：
5.1
通讯作者：
Martini, Claudia
中科院分区：
文献类型：
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作者：
Daniele, Simona;Pietrobono, Deborah;Martini, Claudia
神经退行性疾病(NDS)的特征是特定蛋白质在大脑和外周组织中异常堆积/错误折叠，主要是α-突触核蛋白(α-syn)、β-淀粉样蛋白(1-42)(Aβ)和tau。除了同源低聚物外，α-syn与Aβ或tau相互作用的作用已逐渐显现。蛋白质积累的改变与氧化应激和身体活动有关；然而，到目前为止，还没有发现外周α-SYN异聚体的存在、抗氧化能力和体育锻炼之间的相关性。本文测定了健康受试者(久坐和运动员)红细胞中α-syn、Aβ、tau及其杂化复合体的含量。这些参数与抗氧化能力(AOC)的程度有关，AOC是衰老相关病理中氧化应激的关键标志，体育锻炼被认为在NDS中起着重要的预防作用，并调节氧化应激。在老年人和久坐不动的受试者中，tau含量和血浆中对羟基自由基的AOC均降低；相反，α-syn和Aβ在老年人中积累，并与羟基AOC和体力活动水平呈负相关。首次对α-syn与Aβ或tau形成的杂化络合物进行了定量，并证明其与羟基AOC呈负相关。此外，运动员的α-SYN/Aβ聚集体显著减少，且与体力活动水平呈负相关，与年龄无关。这些数据证实了抗氧化能力/体力活动与蛋白质积累减少之间的正相关，并提示外周α-SYN异源复合体可能是ND相关蛋白质错误折叠的新指标。
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily alpha-synuclein (alpha-syn), beta-amyloid(1-42) (A beta), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of alpha-syn interactions with A beta 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 alpha-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of alpha-syn, A beta, 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, alpha-syn and A beta accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, alpha-syn heterocomplexes with A beta or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, alpha-syn/A beta 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 alpha-syn heterocomplexes may represent new indicators of ND-related protein misfolding.