@article{oai:nagoya.repo.nii.ac.jp:00031313,
 author = {Ishigaki, Shinsuke and Riku, Yuichi and Fujioka, Yusuke and Endo, Kuniyuki and Iwade, Nobuyuki and Kawai, Kaori and Ishibashi, Minaka and Yokoi, Satoshi and Katsuno, Masahisa and Watanabe, Hirohisa and Mori, Keiko and Akagi, Akio and Yokota, Osamu and Terada, Seishi and Kawakami, Ito and Suzuki, Naoki and Warita, Hitoshi and Aoki, Masashi and Yoshida, Mari and Sobue, Gen},
 issue = {8},
 journal = {Brain},
 month = {Aug},
 note = {Fused in sarcoma (FUS) is genetically and clinicopathologically linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We have previously reported that intranuclear interactions of FUS and splicing factor, proline- and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interaction leads to an increase in the ratio of 4-repeat tau (4R-tau)/3-repeat tau (3R-tau), which manifests in FTLD-like phenotypes in mice. Here, we examined FUS-SFPQ interactions in 142 autopsied individuals with FUS-related ALS/FTLD (ALS/FTLD-FUS), TDP-43-related ALS/FTLD (ALS/FTLD-TDP), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease, or Pick’s disease as well as controls. Immunofluorescent imaging showed impaired intranuclear co-localization of FUS and SFPQ in neurons of ALS/FTLD-FUS, ALS/FTLD-TDP, progressive supranuclear palsy and corticobasal degeneration cases, but not in Alzheimer’s disease or Pick’s disease cases. Immunoprecipitation analyses of FUS and SFPQ revealed reduced interactions between the two proteins in ALS/FTLD-TDP and progressive supranuclear palsy cases, but not in those with Alzheimer disease. Furthermore, the ratio of 4R/3R-tau was elevated in cases with ALS/FTLD-TDP and progressive supranuclear palsy, but was largely unaffected in cases with Alzheimer disease. We concluded that impaired interactions between intranuclear FUS and SFPQ and the subsequent increase in the ratio of 4R/3R-tau constitute a common pathogenesis pathway in FTLD spectrum diseases., ファイル公開日: 2021/08/08},
 pages = {2398--2405},
 title = {Aberrant interaction between FUS and SFPQ in neurons in a wide range of FTLD spectrum diseases},
 volume = {143},
 year = {2020}
}