Alzheimer disease (AD) is a major threat of twenty-first century that is responsible for the majority of dementia in the elderly. Development of effective AD-preventing therapies are the top priority tasks for neuroscience research. Amyloid hypothesis of AD is a dominant idea in the field, but so far all amyloid-targeting therapies have failed in clinical trials. In addition to amyloid accumulation, there are consistent reports of abnormal calcium signaling in AD neurons. AD neurons exhibit enhanced intracellular calcium (Ca(2) (+)) liberation from the endoplasmic reticulum (ER) and reduced store-operated Ca(2) (+) entry (SOC). These changes occur primarily as a result of ER Ca(2) (+) overload. We argue that normalization of intracellular Ca(2) (+) homeostasis could be a strategy for development of effective disease-modifying therapies. The current review summarizes recent data about changes in ER Ca(2) (+) signaling in AD. Ca(2) (+) channels that are discussed in the current review include: inositol trisphosphate receptors, ryanodine receptors, presenilins as ER Ca(2) (+) leak channels, and neuronal SOC channels. We discuss how function of these channels is altered in AD and how important are resulting Ca(2) (+) signaling changes for AD pathogenesis.
Keywords: Alzheimer disease; Ca2+ signaling; dantrolene; endoplasmic reticulum; inositol trisphosphate receptors; presenilins; ryanodine receptors; store-operated Ca2+ channels.