The inositol metabolism pathway as a target for neuroprotective strategies.

Abstract

Neurodegeneration is characterized by the progressive and permanent loss of neurons. Degeneration typically results in a debilitating loss of function in an otherwise healthy person. Neurodegenerative diseases have enormous direct health care costs, with some estimates for diseases, such as Alzheimer's disease exceeding $36,000 USD per patient annually. Currently there is a lack of effective treatments for neurodegenerative disease, thus there is no way to slow or prevent the irreversible death of neurons in patients suffering from these diseases. Growing evidence suggests that the pathways controlling the levels of intracellular calcium [Ca2+], including the second messenger inositol 1,4,5-trisphosphate (InsP3), are disrupted in some of the more common forms of neurodegeneration. Dysfunction in these pathways allow for excessive and toxic levels of intracellular [Ca2+] to accumulate. One possible neuroprotective strategy would be to target InsP3 regulatory pathways to prevent excess calcium release from intracellular stores. This review will focus on the implication of InsP3 pathways in current strategies of neuroprotection. While the causes of neurodegeneration are diverse, common pathological pathways may exist between diseases and protective targeting of a common pathway would have the potential to treat genetically distinct diseases.