| First Author | Vella LJ | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 7 | Pages | 2930-40 |
| PubMed ID | 22490781 | Mgi Jnum | J:319557 |
| Mgi Id | MGI:6861991 | Doi | 10.1096/fj.11-200295 |
| Citation | Vella LJ, et al. (2012) Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments. FASEB J 26(7):2930-40 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. The proteolytic processing of the amyloid precursor protein (APP) into the beta-amyloid (Abeta) peptide is a central event in AD. While the pathway that generates Abeta is well described, many questions remain concerning general APP metabolism and its metabolites. It is becoming clear that the amino-terminal region of APP can be processed to release small N-terminal fragments (NTFs). The purpose of this study was to investigate the occurrence and generation of APP NTFs in vivo and in cell culture (SH-SY5Y) in order to delineate the cellular pathways implicated in their generation. We were able to detect 17- to 28-kDa APP NTFs in human and mouse brain tissue that are distinct from N-APP fragments previously reported. We show that the 17- to 28-kDa APP NTFs were highly expressed in mice from the age of 2 wk to adulthood. SH-SY5Y studies indicate the generation of APP NTFs involves a novel APP processing pathway, regulated by protein kinase C, but independent of alpha-secretase or beta-secretase 1 (BACE) activity. These results identify a novel, developmentally regulated APP processing pathway that may play an important role in the physiological function of APP. |
