Tubulin Polymerization Promoting Protein (TPPP/p25) as a Marker for Oligodendroglial Changes in Multiple Sclerosis
Tubulin Polymerization Promoting Protein (TPPP/p25) as a Marker for Oligodendroglial Changes in Multiple Sclerosis
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DOI：
10.1002/glia.21054
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发表时间：
2010-11-15
期刊：
影响因子：
6.2
通讯作者：
Kovacs, Gabor G.
中科院分区：
文献类型：
--
作者：
Hoeftberger, Romana;Fink, Stephanie;Kovacs, Gabor G.
多发性硬化（MS）是一种中枢神经系统的慢性炎症性脱髓鞘疾病，具有不同程度的髓鞘再生。髓鞘再形成起源于少突胶质细胞（OG）前体细胞，其迁移并分化成成熟OG。微管蛋白聚合促进蛋白（TPPP/p25）位于成熟的OG中，并在多系统萎缩中聚集在少突胶质细胞胞质包涵体中。我们开发了一种新的单克隆抗TPPP/p25抗体，以量化OG在不同亚型和疾病阶段的MS，和可能的退行性变化的OG。我们评估了25例MS病例的尸检材料，包括急性、原发性进行性、继发性进行性、复发缓解型MS和5例对照。脱髓鞘病变显示斑块内TPPP/p25阳性OG丢失。在髓鞘再生过程中，TPPP/p25首先在OG细胞浆中表达，然后在髓鞘中表达。我们观察到MS患者正常外观的白色物质（NAWM）中TPPP/p25免疫反应性OG的数量增加。在MS病例中，与NAWM和斑块相比，OG中TPPP/p25免疫反应的胞质面积在斑块周围区域较高，并且TPPP/p25免疫反应的OG胞质面积与疾病持续时间呈负相关。在具有增大的细胞质的OG中缺乏磷酸-TDP-43、磷酸-tau、α-突触核蛋白和泛素免疫反应性。我们的数据表明受损的分化，迁移和激活能力的OG在MS的后期疾病阶段。上调TPPP/p25在斑块周围白色物质OG没有证据的包涵体形成可能反映了激活状态。TPPP/p25在MS中的独特和增加的表达使其成为MS的潜在预后和诊断标志物。（C）2010 Wiley-Liss，Inc.
Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, alpha-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS. (C) 2010 Wiley-Liss, Inc.