Kawamoto Yasuhiro, Ito Hidefumi, Ihara Masafumi, Takahashi Ryosuke
Clin Neuropathol. 2014 Jan-Feb;33(1):76-83. doi: 10.5414/NP300610.
X-linked inhibitor of apoptosis protein (XIAP) selectively binds to caspases-3, -7 and -9, and inhibits the activities of these caspases. To elucidate the role of XIAP in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. In normal brains, several types of neurons were immunostained for XIAP, and XIAP-immunopositive oligodendrocytes were scattered throughout the cerebral and cerebellar white matter. In the MSA brains, neuronal XIAP immunoreactivity was spared even in the severely-affected lesions, and glial cytoplasmic inclusions (GCIs), neuronal cytoplasmic inclusions (NCIs) and dystrophic neurites were all intensely immunoreactive for XIAP. A semiquantitative analysis of mid-pons sections double-immunostained for XIAP and α-synuclein demonstrated that the average percentages of XIAP-immunopositive GCIs and NCIs in the pontine nucleus were 70.2% and 82.2%, respectively. Our results suggest that a widespread accumulation of XIAP may occur in brains with MSA, and that XIAP may be partially associated with the pathogenesis of MSA.
X连锁凋亡抑制蛋白（XIAP）可选择性地与半胱天冬酶-3、-7和-9结合，并抑制这些半胱天冬酶的活性。为阐明XIAP在多系统萎缩（MSA）患者中的作用，我们对8名正常受试者和10例MSA患者的福尔马林固定、石蜡包埋切片中的XIAP进行了免疫组织化学研究。在正常大脑中，几种类型的神经元对XIAP呈免疫染色阳性，XIAP免疫阳性的少突胶质细胞散在于大脑和小脑白质中。在MSA患者的大脑中，即使在严重受累的病变中，神经元XIAP免疫反应性也得以保留，而胶质细胞质内含物（GCI）、神经元细胞质内含物（NCI）和营养不良性神经突对XIAP均呈强免疫反应性。对脑桥中部切片进行XIAP和α-突触核蛋白双重免疫染色的半定量分析表明，脑桥核中XIAP免疫阳性的GCI和NCI的平均百分比分别为70.2%和82.2%。我们的结果表明，MSA患者大脑中可能广泛存在XIAP积聚，且XIAP可能与MSA的发病机制部分相关。
