Neurogranin

Neurogranin is a neuron-specific, calmodulin-binding protein encoded by the NRGN gene in humans. It is highly enriched in the brain, with strong expression in the cerebral cortex and hippocampus, and localizes to dendritic spines and postsynaptic densities where it participates in calcium-dependent signaling.

Biochemically, neurogranin binds calmodulin in the absence of calcium, effectively sequestering it, and releases calmodulin when calcium levels rise. This dynamic regulation modulates the availability of calmodulin for downstream signaling cascades that drive synaptic plasticity. Neurogranin is known to be phosphorylated by protein kinases such as PKC, which can influence its interaction with calmodulin and its signaling role. Through these mechanisms, neurogranin influences calcium/calmodulin–dependent signaling pathways that contribute to synaptic strength and plasticity, including processes underlying learning and memory.

In humans, alterations in neurogranin expression and processing have been linked to neurological conditions. Cerebrospinal fluid levels of neurogranin fragments are elevated in Alzheimer's disease and related syndromes, reflecting synaptic degeneration. As a biomarker, neurogranin is studied for its potential to indicate synaptic loss and cognitive decline, and research continues to assess its diagnostic and prognostic value. The NRGN gene, encoding the protein, is considered important for proper synaptic function, and changes in its regulation may contribute to neurophysiological differences observed in aging and disease.

Overall, neurogranin serves as a modulator of calmodulin availability at synapses and as a component of the signaling machinery that governs synaptic plasticity, with ongoing investigations into its role as a biomarker and therapeutic target in neurodegenerative conditions.