Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Neurology, National Hospital Organization, Omuta National Hospital, Fukuoka, Japan.
Neuropathology. 2024 Feb;44(1):31-40. doi: 10.1111/neup.12927. Epub 2023 Jun 21.
Neuronal intranuclear inclusions (NIIs) are common key structures in polyglutamine (polyQ) diseases such as Huntington disease (HD), spinocerebellar ataxia type 1 (SCA1), and SCA3. Marinesco bodies (MBs) of dopaminergic neurons in the substantia nigra are also intranuclear structures and are frequently seen in normal elderly people. Ribosomal dysfunction is closely related to two differential processes; therefore, we aimed to identify the pathological characteristics of ribosomal protein SA (RPSA), a ribosomal protein, in both states. To this end, we evaluated the autopsy findings in four patients with HD, two SCA3, and five normal elderly cases (NCs). Immunohistochemical studies demonstrated that both NIIs and MBs contain RPSA. In polyQ diseases, RPSA was co-localized with polyQ aggregations, and 3D-reconstructed images revealed their mosaic-like distribution. Assessments of the organization of RPSA and p62 in NIIs showed that RPSA was more localized toward the center than p62 and that this unique organization was more evident in the MBs. Immunoblotting of the temporal cortices revealed that the nuclear fraction of HD patients contained more RPSA than that of NCs. In conclusion, our study revealed that RPSA is a common component of both NIIs and MBs, indicating that a similar mechanism contributes to the formation of polyQ NIIs and MBs.
神经元核内包涵体(NIIs)是亨廷顿病(HD)、脊髓小脑共济失调 1 型(SCA1)和 SCA3 等多聚谷氨酰胺(polyQ)疾病的常见关键结构。黑质多巴胺能神经元的 Marinesco 体(MBs)也是核内结构,在正常老年人中也经常见到。核糖体功能障碍与两种不同的过程密切相关;因此,我们旨在确定核糖体蛋白 SA(RPSA)的病理特征,核糖体蛋白,在这两种状态下。为此,我们评估了 4 例 HD、2 例 SCA3 和 5 例正常老年病例(NCs)的尸检结果。免疫组织化学研究表明,NIIs 和 MBs 均含有 RPSA。在 polyQ 疾病中,RPSA 与 polyQ 聚集物共定位,3D 重建图像显示其镶嵌式分布。对 NIIs 中 RPSA 和 p62 的组织评估表明,RPSA 比 p62 更靠近中心,这种独特的组织在 MBs 中更为明显。对颞叶皮质的免疫印迹分析表明,HD 患者的核部分比 NCs 含有更多的 RPSA。总之,我们的研究表明 RPSA 是 NIIs 和 MBs 的共同成分,表明类似的机制有助于形成 polyQ NIIs 和 MBs。