Endoplasmic reticulum Ca2+ homeostasis and neuronal death

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Abstract
The endoplasmic reticulum (ER) is a universal signalling organelle, which regulates a wide range of neuronal functional responses. Calcium release from the ER underlies various forms of intracellular Ca2+ signalling by either amplifying Ca2+ entry through voltage‐gated Ca2+ channels by Ca2+‐induced Ca2+ release (CICR) or by producing local or global cytosolic calcium fluctuations following stimulation of metabotropic receptors through inositol‐1,4,5‐trisphosphate‐induced Ca2+ release (IICR). The ER Ca2+ store emerges as a single interconnected pool, thus allowing for a long‐range Ca2+ signalling via intra‐ER tunnels. The fluctuations of intra‐ER free Ca2+ concentration regulate the activity of numerous ER resident proteins responsible for post‐translational protein folding and modification. Disruption of ER Ca2+ homeostasis results in the developing of ER stress response, which in turn controls neuronal survival. Altered ER Ca2+ handling may be involved in pathogenesis of various, neurodegenerative diseases including brain ischemia and Alzheimer dementia.