Calcium dysregulation, IP3 signaling, and Alzheimer's disease.

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.

• Authors: Grace E Stutzmann
• Journal: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry (Neuroscientist) Vol. 11 Issue 2 Pg. 110-5 (Apr 2005) ISSN: 1073-8584 [Print] United States
• PMID: 15746379 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Phosphoric Monoester Hydrolases
• Inositol Polyphosphate 5-Phosphatases
• Calcium

Topics

• Alzheimer Disease (genetics, metabolism, pathology)
• Animals
• Calcium (metabolism)
• Disease Models, Animal
• Humans
• Inositol Polyphosphate 5-Phosphatases
• Mice
• Mice, Transgenic
• Mutation
• Neurons (metabolism, pathology)
• Phosphoric Monoester Hydrolases (metabolism)
• Signal Transduction (physiology)