ER calcium and Alzheimer's disease: In a state of flux

Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalScience Signaling
Volume3
Issue number114
DOIs
StatePublished - Mar 23 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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