Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease

Shinichiro Mori, Hiroyuki Honda, Takashi Ishii, Motoi Yoshimura, Naokazu Sasagasako, Satoshi O. Suzuki, Takayuki Taniwaki, Toru Iwaki

研究成果: Contribution to journalArticle査読

3 被引用数 (Scopus)

抄録

Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2-positive nuclear inclusions in all examined cases. Localization of poly (rC)-binding protein 1 (PCBP1) in 1C2-positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2-positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS-related familial amyotrophic lateral sclerosis.

本文言語英語
ページ(範囲)358-367
ページ数10
ジャーナルNeuropathology
39
5
DOI
出版ステータス出版済み - 10 1 2019

All Science Journal Classification (ASJC) codes

  • 病理学および法医学
  • 臨床神経学

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