Difference between revisions of "Boyle 2012 Brain Res"
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{{Publication | {{Publication | ||
|title=Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C (2012) Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells. Brain Res | |title=Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C (2012) Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells. Brain Res 1443: 75-88 | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/22297172 PMID: 22297172] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/22297172 PMID: 22297172] | ||
|authors=Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C | |authors=Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C | ||
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|journal=Brain Res | |journal=Brain Res | ||
|abstract=Mutations in the presenilin 1 (PS1) gene lead to early-onset Alzheimer's disease with the S170F mutation causing the earliest reported age of onset. Expression of this, and other PS1 mutations, in SH-SY5Y cells resulted in significant loss of cellular viability compared to control cells. Basal Ca(2+) concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca(2+)-free solutions did not deplete Ca(2+) stores, demonstrating there was no difference in Ca(2+) leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca(2+)](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca(2+) store release might be affected in PS1 mutants, store size was similar. However, when Ca(2+)-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ΔE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca(2+) influx pathways. There was no significant effect of any of the mutations on mitochondrial respiration. Amyloid β(Aβ(1-40)) secretion was reduced, and Aβ(1-42) secretion increased in the S170F cells resulting in a very large increase in the Aβ42/40 ratio. This, rather than any potential disruption of ER Ca(2+) stores, is likely to explain the extreme pathology of this mutant. | |abstract=Mutations in the presenilin 1 (PS1) gene lead to early-onset Alzheimer's disease with the S170F mutation causing the earliest reported age of onset. Expression of this, and other PS1 mutations, in SH-SY5Y cells resulted in significant loss of cellular viability compared to control cells. Basal Ca(2+) concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca(2+)-free solutions did not deplete Ca(2+) stores, demonstrating there was no difference in Ca(2+) leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca(2+)](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca(2+) store release might be affected in PS1 mutants, store size was similar. However, when Ca(2+)-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ΔE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca(2+) influx pathways. There was no significant effect of any of the mutations on mitochondrial respiration. Amyloid β(Aβ(1-40)) secretion was reduced, and Aβ(1-42) secretion increased in the S170F cells resulting in a very large increase in the Aβ42/40 ratio. This, rather than any potential disruption of ER Ca(2+) stores, is likely to explain the extreme pathology of this mutant. | ||
|keywords=Alzheimer's disease; presenilin 1 (PS1); Amyloid β Aβ(1-40) and Aβ(1-42); | |keywords=Alzheimer's disease; presenilin 1 (PS1); Amyloid β Aβ(1-40) and Aβ(1-42); | ||
|mipnetlab=UK Leeds Peers C | |mipnetlab=UK Leeds Peers C | ||
}} | }} |
Revision as of 15:32, 3 April 2012
Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C (2012) Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells. Brain Res 1443: 75-88 |
Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C (2012) Brain Res
Abstract: Mutations in the presenilin 1 (PS1) gene lead to early-onset Alzheimer's disease with the S170F mutation causing the earliest reported age of onset. Expression of this, and other PS1 mutations, in SH-SY5Y cells resulted in significant loss of cellular viability compared to control cells. Basal Ca(2+) concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca(2+)-free solutions did not deplete Ca(2+) stores, demonstrating there was no difference in Ca(2+) leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca(2+)](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca(2+) store release might be affected in PS1 mutants, store size was similar. However, when Ca(2+)-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ΔE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca(2+) influx pathways. There was no significant effect of any of the mutations on mitochondrial respiration. Amyloid β(Aβ(1-40)) secretion was reduced, and Aβ(1-42) secretion increased in the S170F cells resulting in a very large increase in the Aβ42/40 ratio. This, rather than any potential disruption of ER Ca(2+) stores, is likely to explain the extreme pathology of this mutant. • Keywords: Alzheimer's disease; presenilin 1 (PS1); Amyloid β Aβ(1-40) and Aβ(1-42);
• O2k-Network Lab: UK Leeds Peers C
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