Calcium Dysregulation, IP3 Signaling, and Alzheimer’s Disease

Publisher Website
Google Scholar
Abstract
Ca2+ ions subserve complex signaling roles in neurons, regulating functions ranging from gene transcription to modulation of membrane excitability. Ca2+ ions enter the cytosol from extracellular sources, such as entry through voltage-gated channels, and by liberation from intracellular endoplasmic reticulum (ER) stores through inositol triphosphate (IP3) receptors and/or ryanodine (RyR) receptors. Disruptions of intracellular Ca2+ signaling are proposed to underlie the pathophysiology of Alzheimer’s disease (AD), and recent studies examining AD-linked mutations in the presenilin genes demonstrate enhanced ER Ca2+ release in a variety of cell types and model systems. The development of transgenic AD mouse models provides a means to study the mechanisms and downstream effects of neuronal ER Ca2+-signaling alterations on AD pathogenesis and offers insight into potential novel therapeutic strategies. The author discusses recent findings in both the physiological functioning of the IP3-signaling pathway in neurons and the involvement of ERCa2+ disruptions in the pathogenesis of AD.