Calcium dysregulation, IP3 signaling, and Alzheimer's disease.
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.
Stutzmann
Grace E
GE
Department of Neurobiology and Behavior, 1146 McGaugh Hall, University of California-Irvine, Irvine, CA 92697, USA. grace@uci.edu
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D002118:Calcium