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  • Title: Ryanodine receptor-mediated interference of neuronal cell differentiation by presenilin 2 mutation.
    Author: Lee SM, Lee JW, Song YS, Hwang DY, Kim YK, Nam SY, Kim DJ, Yun YW, Yoon DY, Hong JT.
    Journal: J Neurosci Res; 2005 Nov 15; 82(4):542-50. PubMed ID: 16240390.
    Abstract:
    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 ryanodine-receptor (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.
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