α-Synuclein is a protein related to synucleinopathies with high expression in the central nervous system and erythrocytes which are a major source of peripheral α-synuclein. Recent reports have suggested the presence of α-synuclein within extracellular vesicles derived from erythrocytes, potentially contributing to the pathogenesis of synucleinopathies. While Lewy bodies, intracellular inclusions containing aggregated α-synuclein, are prominently observed within the brain, their occurrence in peripheral neurons implies the dissemination of synucleinopathy pathology throughout the body via the propagation of α-synuclein. In this study, we found erythrocytes and circulating extracellular vesicles obtained from plasma contained α-synuclein, which was separated into four major forms using high-resolution clear native-PAGE and isoelectric focusing. Notably, erythrocyte α-synuclein was classified into full-length and C-terminal truncated forms, with truncation observed between Y133 and Q134 as determined by LC-MS/MS analysis. Our finding revealed that C-terminally truncated α-synuclein, which was previously reported to exist solely within the brain, was also present in erythrocytes and circulating extracellular vesicles obtained from plasma.

中文翻译：

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C 末端截短是人红细胞 α-突触核蛋白的一种重要翻译后修饰

α-突触核蛋白是一种与突触核蛋白病相关的蛋白质，在中枢神经系统和红细胞中高表达，而红细胞是外周 α-突触核蛋白的主要来源。最近的报告表明，红细胞来源的细胞外囊泡中存在 α-突触核蛋白，可能导致突触核蛋白病的发病机制。虽然路易体（含有聚集的 α-突触核蛋白的细胞内包涵体）在大脑中明显可见，但它们在外周神经元中的出现意味着突触核蛋白病病理学通过 α-突触核蛋白的传播在全身传播。在这项研究中，我们发现从血浆中获得的红细胞和循环细胞外囊泡含有 α-突触核蛋白，使用高分辨率清晰的非变性 PAGE 和等电聚焦将其分为四种主要形式。值得注意的是，红细胞 α-突触核蛋白分为全长形式和 C 端截短形式，通过 LC-MS/MS 分析确定，在 Y133 和 Q134 之间观察到截短。我们的发现表明，C 端截短的 α-突触核蛋白（之前报道仅存在于大脑中）也存在于红细胞和从血浆中获得的循环细胞外囊泡中。