Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Neuropathology. 2013 Jun;33(3):237-45. doi: 10.1111/j.1440-1789.2012.01346.x. Epub 2012 Sep 19.
Alpha-synuclein (αS) is one of the major constituents of Lewy bodies (LBs). Several lines of evidence suggest that the autophagy-lysosome pathway (ALP) is involved in the removal of αS. We have previously reported that granulovacuolar degeneration (GVD) in neurons involved a subunit of the endosomal sorting complexes required for transport (ESCRT). In this study, we examined the association between alpha-synucleinopathy and autophagy through immunohistochemical analysis of charged multivesicular body protein 2B (CHMP2B), a component of the ESCRT-pathway. We examined the brainstems of 17 patients with Parkinson's disease (PD), incidental Lewy body disease (ILBD), multiple system atrophy (MSA), and Alzheimer's disease (AD) immunohistochemically using antibodies against phosphorylated αS (pαS), phosphorylated tau and CHMP2B. LBs and a proportion of glial cytoplasmic inclusions (GCIs) were immunopositive for pαS and CHMP2B. Neurons containing CHMP2B-immunoreactive granules were detected in PD and ILBD, but not in MSA and AD brains. CHMP2B immunoreactivity was increased in the dorsal motor nucleus of the vagus nerve (DMNX) in PD and ILBD brains, relative to that in MSA and AD. These findings indicate that the ESCRT-pathway is implicated in the formation of αS inclusions, especially in PD and ILBD.
α-突触核蛋白（αS）是路易体（LB）的主要成分之一。有几条证据表明自噬溶酶体途径（ALP）参与了αS 的清除。我们之前曾报道过，神经元中的颗粒空泡变性（GVD）涉及到内体分选复合物必需的运输亚基（ESCRT）的一个亚单位。在这项研究中，我们通过对参与 ESCRT 途径的内体分选复合物必需的运输亚基的一个亚单位电荷多泡体蛋白 2B（CHMP2B）的免疫组织化学分析，研究了α-突触核蛋白病与自噬之间的关系。我们使用针对磷酸化的 αS（pαS）、磷酸化的 tau 和 CHMP2B 的抗体，对 17 例帕金森病（PD）、偶然发现的路易体病（ILBD）、多系统萎缩（MSA）和阿尔茨海默病（AD）患者的脑干进行了免疫组织化学检查。LB 和一部分神经胶质细胞质包涵体（GCIs）对 pαS 和 CHMP2B 呈免疫阳性。在 PD 和 ILBD 中，含有 CHMP2B 免疫反应性颗粒的神经元被检测到，但在 MSA 和 AD 脑中未被检测到。与 MSA 和 AD 相比，PD 和 ILBD 大脑的迷走神经背核（DMNX）中 CHMP2B 免疫反应性增加。这些发现表明，ESCRT 途径与 αS 包涵体的形成有关，特别是在 PD 和 ILBD 中。
