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Sci. Signal., 23 March 2010
Vol. 3, Issue 114, p. pe10
[DOI: 10.1126/scisignal.3114pe10]


ER Calcium and Alzheimer’s Disease: In a State of Flux

Mark P. Mattson*

Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.

Abstract: The calcium ion (Ca2+) plays fundamental roles in orchestrating dynamic changes in the function and structure of nerve cell circuits in the brain. The endoplasmic reticulum (ER), an organelle that actively removes Ca2+ from the cytoplasm, can release stored Ca2+ through ER membrane receptor channels responsive either to the lipid messenger inositol trisphosphate(IP3) or to cytosolic Ca2+. Emerging findings suggest that perturbed ER Ca2+ homeostasis contributes to the dysfunction and degeneration of neurons that occurs in Alzheimer’s disease (AD). Presenilin-1 (PS1) is an integral membrane protein in the ER; mutations in PS1 that cause early-onset inherited AD increase the pool of ER Ca2+ available for release and also enhance Ca2+ release through ER IP3- and ryanodine-sensitive channels. By enhancing Ca2+ flux across the ER membrane, PS1 mutations may exaggerate Ca2+ signaling in synaptic terminals and thereby render them vulnerable to dysfunction and degeneration in the settings of aging and amyloid accumulation in AD.

* Corresponding author. E-mail, mattsonm{at}

Citation: M. P. Mattson, ER Calcium and Alzheimer’s Disease: In a State of Flux. Sci. Signal. 3, pe10 (2010).

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