Role of STIM1 in neurodegeneration

STIM1 is an endoplasmic reticulum (ER) protein with a key role in Ca²⁺ mobilization. Due to its ability to act as an ER-intraluminal Ca²⁺ sensor, it regulates store-operated Ca²⁺ entry (SOCE), which is a Ca²⁺ influx pathway involved in a wide variety of signalling pathways in eukaryotic cells. Despite its important role in Ca²⁺ transport, current knowledge about the role of STIM1 in neurons is much more limited. Growing evidence supports a role for STIM1 and SOCE in the preservation of dendritic spines required for long-term potentiation and the formation of memory. In this regard, recent studies have demonstrated that the loss of STIM1, which impairs Ca²⁺ mobilization in neurons, risks cell viability and could be the cause of neurodegenerative diseases. The role of STIM1 in neurodegeneration and the molecular basis of cell death triggered by low levels of STIM1 are discussed in this review.