Neuronal calcium signaling via store-operated channels in health and disease.

Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca) into cells in response to the depletion of intracellular Ca stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca sensor STIM1 and plasma membrane Ca channel Orai1 and serves to sustain Ca signaling and refill ER Ca stores. In contrast, because of the complexity of Ca influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent. This review summarizes the available data on the molecular components of nSOCE and their relevance to neuronal signaling. We also present evidence of disturbances of nSOCE in neurodegenerative diseases (namely Alzheimer's disease, Huntington's disease, and Parkinson's disease) and traumatic brain injury. The emerging important role of nSOCE in neuronal physiology and pathology makes it a possible clinical target.