| First Author | Hou P | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 3 | Pages | 1310-5 |
| PubMed ID | 25557959 | Mgi Jnum | J:221689 |
| Mgi Id | MGI:5641315 | Doi | 10.1016/j.neurobiolaging.2014.12.005 |
| Citation | Hou P, et al. (2015) Role of copper and the copper-related protein CUTA in mediating APP processing and Abeta generation. Neurobiol Aging 36(3):1310-5 |
| abstractText | One major pathologic hallmark and trigger of Alzheimer's disease (AD) is overproduction and accumulation of beta-amyloid (Abeta) species in the brain. Abeta is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases. Abnormal copper homeostasis also contributes to AD pathogenesis. Recently, we find that a copper-related protein, CutA divalent cation tolerance homolog of Escherichia coli (CUTA), interacts with the beta-secretase beta-site APP cleaving enzyme 1 (BACE1) and inhibits APP beta-processing and Abeta generation. Herein, we further found that overexpression of CUTA increases intracellular copper level, whereas copper treatments promote CUTA expression. We also confirmed that copper treatments promote APP expression and Abeta secretion. In addition, copper treatments promoted the increase of Abeta secretion induced by CUTA downregulation but had no effect on CUTA-beta-site APP cleaving enzyme 1 interaction. On the other hand, CUTA overexpression ameliorated copper-induced Abeta secretion but had no effect on APP expression. Moreover, we found that Abeta treatments can reduce both CUTA and copper levels in mouse primary neurons. Consistently, both CUTA and copper levels were decreased in the hippocampus of APP/PS1 AD mouse brain. Together, our results reveal a reciprocal modulation of copper and CUTA and suggest that both regulate Abeta generation through different mechanisms, although Abeta mutually affects copper and CUTA levels. |
