PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release.
Explore the source record for details and available documents.
Amyloid beta-Peptides↗
Biomedical subjects
Dae Youn Hwang
Publications and source records attributed to Dae Youn Hwang.
Ryanodine receptor-mediated interference of neuronal cell differentiation by presenilin 2 mutation.
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.
Animals↗
Decrease in NF-kappaB, AP-1 and SP-1 activities in neuronal cells expressing presenilin 2.
Decreases in activities of the NF-kappaB, AP-1 and SP-1 transcription factors, which could act as antiapoptotic factors, in the presenilin 2 transfected PC12 cells, either in nontreatment conditions or under apoptotic stimulation, were found in this study. Similar results were also found in mice brain cells carrying presenilin 2, especially in the mutant gene expressed ones. These findings suggested that presenilin 2 may be implicated in neuronal cell death by altering the antiapoptotic activity of the transcription factors.
Animals↗
Mutant presenilin 2 increases acetylcholinesterase activity in neuronal cells.
A presenilin 2 mutation is believed to be involved in the development of Alzheimer's disease. In addition, transgenic mice with a presenilin 2 mutation have been reported to have learning and memory impairments. In this study, exposing PC12 cells expressing mutant presenilin 2 to 50 microM AP25-35, 30 mM L-glutamate and 50 microM H2O2 caused a significant increase in acetylcholine esterase activity. An in vivo study revealed high levels of this enzyme activity in the mutant presenilin 2 transgenic brains compared with the wild type presenilin 2 transgenic and nontransgenic samples. These results suggest that a mutant presenilin 2-induced neurodegeneration in Alzheimer's disease might be involved in the increase in acetylcholinesterase activity. These findings might help in the development of an appropriate therapeutic intervention targeting mutant presenilin 2-induced Alzheimer's disease.
Acetylcholinesterase↗