Ryanodine receptor-mediated interference of neuronal cell differentiation by presenilin 2 mutation

✍ Scribed by Sang Min Lee; Jae Woong Lee; Youn Sook Song; Dae Youn Hwang; Yong Kyu Kim; Sang Yun Nam; Dae Joong Kim; Young Won Yun; Do Young Yoon; Jin Tae Hong

• Book ID: 102385339
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 478 KB
• Volume: 82
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20655

✦ Synopsis

Neuronal cell differentiation alterations induced by mutant presenilin 2 (PS2) were investigated in transgenic mice expressing wild-type or mutant-type PS2. Progressive increases in differentiation and marker protein expression were found in neuronal cells expressing wild-type PS2, whereas these processes were much perturbed in mutant-type PS2 with elevated ryanodinereceptor (RyR) expression and intracellular calcium levels. Moreover, dantrolene, a blocker of RyR reduced the PS2 mutation-induced interference of cell differentiation and calcium release, but caffeine, an activator of RyR, exacerbated PS2 mutation-induced interference with cell differentiation. Our results indicate that mutant PS2 inhibits normal neuronal cell differentiation and that RyR-mediated calcium overrelease may be a significant factor. V