Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.
Acta Histochem Cytochem. 2010 May 1;43(2):69-75. doi: 10.1267/ahc.10005. Epub 2010 Apr 21.
Recent studies have suggested implications for α-synuclein cytotoxicity in the pathomechanism of multiple system atrophy (MSA). Given in vitro evidence that α-synuclein generates oxidative stress, it is proposed that lipid peroxidation may be accelerated in MSA. To address this issue, we performed an immunohistochemical analysis of protein-bound 4-hydroxy-2-nonenal (P-HNE) in sections of archival, formalin-fixed, paraffin-embedded pontine materials of eight sporadic MSA patients and eight age-matched control subjects. In the MSA cases, P-HNE immunoreactivity was localized in all of the neuronal cytoplasmic inclusions and glial cytoplasmic inclusions, both of them identified with α-synuclein and ubiquitin. It was also detectable in reactive astrocytes and phagocytic microglia but undetectable in activated microglia. By contrast, P-HNE immunoreactivity in the control cases was only very weak or not at all in the parenchyma including neurons and glia. The present results provide in vivo evidence that HNE participates in α-synuclein-induced cytotoxicity and neuroinflammation in MSA.
最近的研究表明，α-突触核蛋白的细胞毒性在多系统萎缩（MSA）的发病机制中具有重要意义。鉴于α-突触核蛋白在体外产生氧化应激的证据，有人提出MSA 中的脂质过氧化可能会加速。为了解决这个问题，我们对 8 例散发性 MSA 患者和 8 例年龄匹配的对照组尸检存档的福尔马林固定石蜡包埋脑桥标本进行了蛋白结合 4-羟基-2-壬烯醛（P-HNE）的免疫组化分析。在 MSA 病例中，P-HNE 免疫反应性定位于所有神经元细胞质包涵体和神经胶质细胞质包涵体，这两种包涵体均与α-突触核蛋白和泛素结合。在反应性星形胶质细胞和吞噬性小胶质细胞中也可检测到，但在活化的小胶质细胞中不可检测到。相比之下，在对照组病例中，P-HNE 免疫反应性在包括神经元和神经胶质细胞在内的实质中非常弱或根本不存在。本研究结果提供了体内证据，表明 HNE 参与了 MSA 中 α-突触核蛋白诱导的细胞毒性和神经炎症。
