Ribosomal protein SA is a common component of neuronal intranuclear inclusions in polyglutamine diseases and Marinesco bodies

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.

Automated summary

Neuronal intranuclear inclusions (NIIs) and Marinesco bodies (MBs) both contain ribosomal protein SA (RPSA) and are related to polyglutamine diseases and aging. RPSA is co-localized with polyQ aggregations in NIIs, and its distribution is mosaic-like. The unique organization of RPSA and p62 suggests a common mechanism in the formation of NIIs and MBs. The nuclear fraction of RPSA is increased in HD patients compared to normal elderly individuals.