| First Author | Uchida Y | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 5 | Pages | 1718-26 |
| PubMed ID | 23499467 | Mgi Jnum | J:195338 |
| Mgi Id | MGI:5478646 | Doi | 10.1016/j.ajpath.2013.01.014 |
| Citation | Uchida Y, et al. (2013) Calsyntenin-3 C-terminal fragment accumulates in dystrophic neurites surrounding abeta plaques in tg2576 mouse and Alzheimer disease brains: its neurotoxic role in mediating dystrophic neurite formation. Am J Pathol 182(5):1718-26 |
| abstractText | Dystrophic neurites surrounding beta-amyloid (Abeta) plaques precede neuronal death in Alzheimer disease. These neuritic alterations may be one of the initial stages for synaptic loss and dysfunction. However, intracellular pathways that cause local disruption of neuronal processes by Abeta remain to be fully elucidated. The identification of Abeta-induced genes that mediate neuritic pathology would provide considerable insight into the mechanisms of Alzheimer's disease. Previously, we reported that selective up-regulation of calsyntenin-3 (Cst-3) by Abeta and accumulation of neurotoxic Cst-3 in dystrophic neurites surrounding Abeta plaques may lead to local disruption of these neurites. Like amyloid precursor protein, Cst-3 undergoes two-step proteolytic processing: the primary cleavage with alpha-secretase generates an N-terminal ectodomain and a C-terminal fragment (CTF). The CTF is subsequently cleaved into p3 peptide and an intracellular domain via gamma-secretase. It would be interesting to know whether accumulated Cst-3 in dystrophic neurites surrounding Abeta plaques is the full-length version or a CTF. Herein, we show that the CTF but not full-length Cst-3 accumulated in dystrophic neurites surrounding Abeta plaques in Tg2576 mouse and Alzheimer disease brains. In vitro experiments with Cst-3 fragments have revealed that only the CTF resulted in acceleration of neuronal death. These results indicate that accumulation of the neurotoxic CTF in neurites surrounding Abeta plaques may lead to local disruption of neuronal processes and development of dystrophic neurites. |
