Abstract:

The progressive and permanent loss of neurons that is commonly referred to as neurodegeneration is a phenotypic characteristic of a large group of genetically heterogeneous diseases with clinically distinct pathologies reflective of the function of the neuron affected. Degeneration typically results in a debilitating loss of function inan otherwise healthy person. Neurodegenerative diseases have enormous direct health care costs, with some estimates for diseases, such as Alzheimer’s exceeding $36,000 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+]i, including the second messenger inositol 1,4,5-trisphosphate (InsP3), are disrupted in some of the more common forms of neurodegeneration. Dysfunction in these pathway allow for excessive, toxic levels of [Ca2+]i 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 current strategies of neuroprotection that involve the soluble InsP3 pathways. While the causes of neurodegeneration are diverse, common pathological pathways may exist between diseases, protective targeting of a common pathway would have the potential to treat genetically distinct diseases.