| First Author | Ohno M | Year | 2014 |
| Journal | Neurobiol Aging | Volume | 35 |
| Issue | 1 | Pages | 213-22 |
| PubMed ID | 23954170 | Mgi Jnum | J:211980 |
| Mgi Id | MGI:5577042 | Doi | 10.1016/j.neurobiolaging.2013.07.014 |
| Citation | Ohno M, et al. (2014) Nardilysin prevents amyloid plaque formation by enhancing alpha-secretase activity in an Alzheimer's disease mouse model. Neurobiol Aging 35(1):213-22 |
| abstractText | Amyloid beta (Abeta) peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. Alpha-cleavage of APP by alpha-secretase has a potential to preclude the generation of Abeta because it occurs within the Abeta domain. We previously reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances alpha-cleavage of APP, which results in the decreased generation of Abeta in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents Abeta deposition in the AD mouse model. The activity of alpha-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. However, reactive gliosis adjacent to the Abeta plaques, one of the pathological features of AD, was not affected by the overexpression of NRDc. Taken together, our results indicate that NRDc controls Abeta formation through the regulation of alpha-secretase. |
