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

The inositol 1,4,5-trisphosphate receptor (IP3 R) 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 IP3 R subtypes have been identified in mammalian cells and the predominant isoform in neurons is IP3 R type 1. Dysfunction of IP3 R type 1 may play a role in the pathogenesis of certain neurodegenerative diseases as enhanced activity of the IP3 R was observed in models of Huntington's disease, spinocerebellar ataxias and Alzheimer's disease. These results suggest that IP3 R-mediated signaling is a potential target for treatment of these disorders. In this review we discuss the structure, functions and regulation of the IP3 R in healthy neurons and in conditions of neurodegeneration.