Calcium dysregulation, IP3 signaling, and Alzheimer's disease - PubMed (original) (raw)
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Calcium dysregulation, IP3 signaling, and Alzheimer's disease
Grace E Stutzmann. Neuroscientist. 2005 Apr.
Abstract
Ca(2+) ions subserve complex signaling roles in neurons, regulating functions ranging from gene transcription to modulation of membrane excitability. Ca(2+) 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 (IP(3)) receptors and/or ryanodine (RyR) receptors. Disruptions of intracellular Ca(2+) 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 Ca(2+) 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 Ca(2+)-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 IP(3)-signaling pathway in neurons and the involvement of ERCa(2+) disruptions in the pathogenesis of AD.
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