Role of Endoplasmic Reticulum-Mediated Ca2+ Signaling in Neuronal Cell Death

Significance: Properly controlled intracellular Ca2+ dynamics is crucial for regulation of neuronal function and survival in the central nervous system. The endoplasmic reticulum (ER), a major intracellular Ca2+ store, plays a critical role as a source and sink for neuronal Ca2+. Recent Advances: Accumulating evidence indicates that disrupted ER Ca2+ signaling is involved in neuronal cell death under various pathological conditions, providing novel insight into neurodegenerative disease mechanisms. Critical Issues: We summarize current knowledge concerning the relationship between abnormal ER Ca2+ dynamics and neuronal cell death. We also introduce recent technical advances for probing ER intraluminal Ca2+ dynamics with unprecedented spatiotemporal resolution. Future Directions: Further studies on ER Ca2+ signaling are expected to provide progress for unmet medical needs in neurodegenerative disease.