| First Author | Tanji K | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 470 |
| Issue | 3 | Pages | 635-642 |
| PubMed ID | 26797281 | Mgi Jnum | J:233339 |
| Mgi Id | MGI:5781275 | Doi | 10.1016/j.bbrc.2016.01.093 |
| Citation | Tanji K, et al. (2016) The role of NUB1 in alpha-synuclein degradation in Lewy body disease model mice. Biochem Biophys Res Commun 470(3):635-42 |
| abstractText | Abnormal alpha-synuclein is deposited in neuronal cytoplasmic inclusions and presynapses in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Previously we have shown that NUB1 is accumulated in these specific regions together with abnormal alpha-synuclein and that NUB1 is able to inhibit alpha-synuclein aggregation in cultured cells. We therefore created transgenic (Tg) mice expressing both NUB1 and abnormal alpha-synuclein to investigate the role of NUB1 on degradation of abnormal alpha-synuclein in vivo. Immunohistochemical and biochemical studies confirmed that NUB1 was over-expressed in neurons of mice expressing NUB1 (NUB1 Tg), and both NUB1 and abnormal alpha-synuclein (double Tg). NUB1 levels were increased by 4.7-fold in NUB1 Tg mice compared with wild type mice. Unexpectedly, normal and abnormal alpha-synuclein levels were unchanged between abnormal alpha-synuclein Tg mice (Lewy body disease model mice) and double Tg mice, and pathological observations were almost similar between them. Finally, we found that the levels of insoluble alpha-synuclein were lower and those of some chaperone molecules were higher in double Tg mice compared with abnormal alpha-synuclein Tg mice. These results suggest that increased levels of NUB1 play a potential role in degradation of detergent-insoluble alpha-synuclein in vivo, although it is insufficient to degrade abnormal alpha-synuclein in Lewy body disease model mice. |
