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

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.

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.

Further studies on ER Ca²⁺ signaling are expected to provide progress for unmet medical needs in neurodegenerative disease. Antioxid. Redox Signal. 29, 1147-1157.