Inositol 1,4,5-trisphosphate receptors and neurodegenerative disorders

The inositol 1,4,5-trisphosphate receptor (IP₃R) is an intracellular ion channel that mediates the release of calcium ions from the endoplasmic reticulum. It plays a role in basic biological functions, such as cell division, differentiation, fertilization and cell death, and is involved in developmental processes including learning, memory and behavior. Deregulation of neuronal calcium signaling results in disturbance of cell homeostasis, synaptic loss and dysfunction, eventually leading to cell death. Three IP₃R subtypes have been identified in mammalian cells and the predominant isoform in neurons is IP₃R type 1. Dysfunction of IP₃R type 1 may play a role in the pathogenesis of certain neurodegenerative diseases as enhanced activity of the IP₃R was observed in models of Huntington's disease, spinocerebellar ataxias and Alzheimer's disease. These results suggest that IP₃R-mediated signaling is a potential target for treatment of these disorders. In this review we discuss the structure, functions and regulation of the IP₃R in healthy neurons and in conditions of neurodegeneration.