Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy
Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy
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DOI：
10.1007/s00401-003-0702-5
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发表时间：
2003-07-01
影响因子：
12.7
通讯作者：
Oda, M
中科院分区：
文献类型：
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作者：
Komori, T;Ishizawa, K;Oda, M
胶质细胞质内含物（GCI）是多系统萎缩（MSA）的组织学标志。在 6 名 MSA 患者死后大脑中，在 GCI 中发现了 14-3-3-蛋白免疫反应性，主要存在于基底前脑和小脑的白质组织中。使用双重免疫组织化学，证实了 14-3-3-蛋白和 α-突触核蛋白免疫反应性在 GCI 中的共定位。 14-3-3 蛋白 GCI 的免疫标记率因地区而异，约为 40% 至 90%。半定量分析显示组织变性程度与 14-3-3-蛋白免疫反应性 GCI 密度之间存在显着负相关。 14-3-3 蛋白是通过与靶蛋白中的磷酸化基序结合参与细胞调节的活性辅因子，α-突触核蛋白是 14-3-3 的已知靶点：我们的研究表明，14-3-3 蛋白与 GCI 中的 α-突触核蛋白密切相关，并且 14-3-3 蛋白可能是 GCI 形成中 α-突触核蛋白的候选辅因子。
Glial cytoplasmic inclusions (GCIs) are the histological hallmark of multiple system atrophy (MSA). In six postmortem brains of patients with MSA, 14-3-3-protein immunoreactivity was identified in GCIs predominately in the white matter tissue of the basal forebrain and cerebellum. Using double immunohistochemistry, co-localization of 14-3-3-protein and alpha-synuclein immunoreactivities in the GCIs was confirmed. The immunolabeling rate of GCIs with 14-3-3 proteins varied regionally from approximately 40% to 90%. Semiquantitative analysis yielded a significant negative correlation between degree of tissue degeneration and density of 14-3-3-protein-immunoreactive GCIs. The 14-3-3 proteins are active cofactors involved in cellular regulation through binding to phosphorylated motifs in target proteins and alpha-synuclein is a known target of 14-3-3: Our study suggests that 14-3-3 proteins are closely associated with alpha-synuclein in GCIs and 14-3-3 proteins may be candidate cofactors of alpha-synuclein in GCI formation.