Calcium Dysregulation, IP3 Signaling, and Alzheimer’s Disease

• Published in: The Neuroscientist (Baltimore, Md.) Vol. 11; no. 2; pp. 110 - 115
• Main Author: Stutzmann, Grace E.
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01-04-2005
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Animals; Calcium - metabolism; Disease Models, Animal; Humans; Inositol Polyphosphate 5-Phosphatases; Mice; Mice, Transgenic; Mutation; Neurons - metabolism; Neurons - pathology; Phosphoric Monoester Hydrolases - metabolism; Signal Transduction - physiology; Presenilin; Transgenic; Ryanodine; Neurodegenerative; Endoplasmic reticulum
• ISSN: 1073-8584; 1089-4098
• DOI: 10.1177/1073858404270899

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.