Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy
Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy
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DOI：
10.1007/s00401-003-0726-x
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发表时间：
2003-09-01
影响因子：
12.7
通讯作者：
Trojanowski, JQ
中科院分区：
文献类型：
--
作者：
Giasson, BI;Mabon, ME;Trojanowski, JQ
多系统萎缩（MSA）是一种神经退行性疾病，其特征是胶质细胞质包涵体（GCIs）的存在，其由蛋白α -突触核蛋白（α -syn）的原纤维组成。越来越多的证据表明，这些病变的形成导致细胞功能障碍和变性。导致gci堡垒国家的事件仍然知之甚少。这可能是细胞质环境的变化，可能是α -syn相互作用蛋白的异常表达，可以促进α -syn的聚合。在一些研究中已经报道了GCIs中微管结合蛋白tau的存在，但这些发现并不一致，而且这些研究是在使用抗α -syn抗体检测GCIs的更敏感方法可用之前进行的。近年来，在路易小体中发现了14-3-3蛋白，它们可能是α -syn相互作用的伙伴，也是由α -syn组成的病理包涵体。本研究对21例MSA患者gci中tau和14-3-3蛋白的存在进行了研究。对于大多数病例，tau和14-3-3蛋白仅在gci的一个子集中检测到。在某些情况下，gci中不含14-3-3或tau。当存在于gci时，磷酸化特异性抗体证明tau处于低磷酸化状态。没有14-3-3或tau的α -同步纤维形成似乎足以形成GCI，尽管GCI中多功能蛋白（如14-3-3）的积累可能导致细胞稳态的破坏。
Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the presence of glial cytoplasmic inclusions (GCIs), which are comprised of fibrils of the protein alpha-synuclein (alpha-syn). Increasing evidence indicate that the formation of these lesions leads to cellular dysfunction and degeneration. The events that result in the fort-nation of GCIs remain poorly understood. It is possible that changes in the cytoplasmic milieu, perhaps the aberrant expression of alpha-syn-interacting proteins, can promote the polymerization of alpha-syn. The presence of the microtubule-binding protein, tau, in GCIs has been reported in some studies, but these findings have not been consistent, and these studies were performed prior to the availability of the more sensitive methods of detecting GCIs using anti-alpha-syn antibodies. Recently, 14-3-3 proteins, putative alpha-syn-interacting partners, have been reported in Lewy bodies, which also are pathological inclusions comprised of alpha-syn. In this study the presence of tau and 14-3-3 proteins in GCIs of 21 patients with MSA was investigated. For the majority of cases, tau and 14-3-3 proteins were detected only in a subset of GCIs. In some cases none of the GCIs contained 14-3-3 or tau. When present in GCIs, tau was in a hypophosphorylated state as demonstrated with phosphorylation-specific antibodies. alpha-syn fibrillogenesis without 14-3-3 or tau appears to be sufficient for GCI formation, although it is possible that the accumulation of multi-functional proteins, like 14-3-3, in GCIs contribute to the disruption of cellular homeostasis.