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monSTIM1 is an optogenetic actuator designed to modulate intracellular calcium signaling by activating the store-operated calcium entry (SOCE) pathway. It consists of a monomeric fragment of the **Stromal Interaction Molecule 1 (STIM1)** protein, typically the cytoplasmic C-terminal domain (such as the SOAR/CAD domain), fused to a light-sensitive module like **Cryptochrome 2 (CRY2)**. Upon exposure to blue light, the light-sensitive modules undergo oligomerization, which clusters the attached STIM1 fragments. This clustering mimics the natural activation of endogenous STIM1, allowing it to bind and activate **Orai1** calcium channels on the plasma membrane, thereby inducing a transient influx of Ca2+. In preclinical research, particularly in models of **Alzheimer's disease**, monSTIM1 is used to selectively enhance astrocytic calcium influx, which has been shown to reduce amyloid-beta pathology, mitigate sleep disturbances, and modulate tonic GABA currents in the brain.
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