| First Author | Yun SM | Year | 2013 |
| Journal | Neurobiol Aging | Volume | 34 |
| Issue | 3 | Pages | 650-62 |
| PubMed ID | 22975420 | Mgi Jnum | J:194511 |
| Mgi Id | MGI:5473955 | Doi | 10.1016/j.neurobiolaging.2012.08.005 |
| Citation | Yun SM, et al. (2013) SUMO1 modulates Abeta generation via BACE1 accumulation. Neurobiol Aging 34(3):650-62 |
| abstractText | Accumulation of disease-related proteins is a characteristic event observed in the pathogenesis of neurodegenerative diseases. beta-secretase (BACE)-1, which initiates generation of beta-amyloid (Abeta), is increased in the Alzheimer's diseased brain. However, the mechanisms of BACE1 accumulation in Alzheimer's disease are largely unknown. In this report, we found that small ubiquitin-like modifier (SUMO)-1 interacts with the dileucine motif of BACE1 and regulates the level of BACE1 protein. This was proved by the coimmunoprecipitation, and gain or loss of function experiments. Altering 3 SUMO isoforms affects BACE1 protein levels, and consequently results in altered amyloid precursor protein processing and Abeta generation. BACE1 levels were increased in response to Abeta or apoptosis, but not in cells lacking SUMO1. Abeta increased SUMO1 protein levels in rat cortical neurons. Moreover, SUMO1 immunoreactivity was increased in the amyloid precursor protein transgenic mice. Furthermore, the C-terminus fragments of BACE1 containing dileucine motif reduced Abeta generation by SUMO1 overexpression. Our study indicates SUMO1 is not only a novel and potent regulator of BACE1 accumulation and Abeta generation but also a potential therapeutic target for Alzheimer's disease. |
