Other
12 Authors
- Ohta Y,
- Li X,
- Morihara R,
- Feng T,
- Liu X,
- Nakano Y,
- Fukui Y,
- Shang J,
- Hishikawa N,
- Abe K,
- Huang Y,
- Yamashita T
| First Author | Shang J | Year | 2017 |
| Journal | Neuroscience | Volume | 350 |
| Pages | 158-168 | PubMed ID | 28344074 |
| Mgi Jnum | J:244047 | Mgi Id | MGI:5912826 |
| Doi | 10.1016/j.neuroscience.2017.03.024 | Citation | Shang J, et al. (2017) Aberrant distributions of nuclear pore complex proteins in ALS mice and ALS patients. Neuroscience 350:158-168 |
| abstractText | Nuclear pore complexes (NPCs) play important roles in traffic of molecules between the nucleus and cytoplasm, aberrant distributions of components of NPCs were demonstrated in C9orf72 amyotrophic lateral sclerosis (C9-ALS) patients, but it is elusive whether such abnormities are also the case with other cause of ALS disease. In the present study, we investigated the spatiotemporal distributions of RanGAP1 and 4 representative nucleoporins (GP210, NUP205, NUP107 and NUP50) of NPCs in human Cu/Zn superoxide dismutase-1 mutation transgenic (SOD1-Tg) mice and sporadic ALS patients. Compared with wild type (WT), these proteins displayed age-dependent and progressive nuclear precipitations, and cytoplasmic aberrant expressions in motor neurons of lumbar cord in SOD1-Tg mice from 10 to 18weeks (W). Double immunofluorescent analysis showed abnormal nuclear retention and apparent co-localizations of RanGAPl with NUP205 and NUP205 with NUPl07, meanwhile, GP210 with NUP205 mainly co-localized in the nuclear envelope (NE) of motor neurons. Furthermore, RanGAP1, GP210 and NUP50 showed similarly abnormal nuclear precipitations and cytoplasmic upregulations in SOD1-Tg mice and ALS patients, moreover, aberrant co-localizations of RanGAP1 with TDP-43 and NUP205 with TDP-43 were also observed in motor neurons. The present study indicated that the mislocalization of these proteins of NPCs may underlie the pathogenesis of ALS both in SOD1-Tg mice and human sporadic ALS patients, and these dysfunctions may be a fundamental pathway for ALS that is not specific only in C9-ALS but also in SOD1-ALS, which may be amenable to pharmacotherapeutic intervention. |
