Familial Alzheimer's disease-linked presenilin-1 mutation M146V affects store-operated calcium entry: does gain look like loss?

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to neuron death and synapse loss in the hippocampus and cortex, with consequent cognitive disability and dementia. Mutations in the presenilin-1 (PS1) gene lead to familial Alzheimer's disease (FAD). Here, we report that the expression of FAD-linked PS1 M146V mutant affects store-operated calcium channel activity (Isoc) in human neuroblastoma SK-N-SH cells. Electrophysiological measurements and calcium imaging experiments have revealed the emergent role of calcium sensor STIM2 in the inhibition of calcium release-activated calcium channel activity (Icrac) and enhancement of intracellular Ca(2+) stores content due to PS1 M146V mutant expression. In general, the results of this study suggest that the pathological inhibition of one type of store-operated calcium channels caused by FAD PS1 mutant expression may be accounted for by preceding gain of spontaneous activity of store-operated calcium channels driven by STIM2. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Citation

M Ryazantseva, K Skobeleva, E Kaznacheyeva. Familial Alzheimer's disease-linked presenilin-1 mutation M146V affects store-operated calcium entry: does gain look like loss? Biochimie. 2013 Jul;95(7):1506-9

PMID: 23624206

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