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Neuronal Calcium Signaling and Alzheimer’s Disease

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Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 740))

Abstract

Calcium plays a major role in normal functioning of the cells. Deregulation of calcium-mediated signaling has been implicated in many neurodegenerative diseases including Alzheimer’s disease. Studies in neurons and mice expressing Alzheimer’s disease-associated transgenes have shown that the expression of familial Alzheimer’s disease (FAD) mutants of presenilin (PS) and amyloid precursor protein (APP) alter calcium homeostasis and cause synaptic dysfunction and dendritic spine loss in neurons. Mechanistic studies have shown that FAD mutants of presenilin can affect the intracellular calcium levels by affecting the ER calcium stores. A function for presenilins as ER calcium leak channels has been established and studies show that presenilins affect ER calcium load through an effect on IP3 receptors, ryanodine receptors, or SERCA pumps. Even in the absence of an active gamma-secretase complex, presenilins seem to affect calcium homeostasis suggesting that these two functions of presenilins are independent of each other. Studies using FAD mutants of APP have shown that unlike presenilins, FAD-APP do not affect calcium homeostasis in the absence of Aβ. Both Aβ and presenilins seem to affect calcium homeostasis at very early stages of disease development affecting the synaptic transmission and function prior to neuritic plaque development. Altered calcium signaling differentially regulates genes such as calcineurin, calmodulin kinase II, MAP kinase etc and induces protein modifications and neurite degeneration. Since functional synapses and synaptic transmission are fundamental processes in memory formation, alterations in these processes can lead to neuronal dysfunction and memory deficit as seen in Alzheimer’s disease. This chapter gives an overview of calcium signaling in different systems, specifically neurons, the functioning of pre- and post-synaptic signaling, and how their deregulation influences pathology development in Alzheimer’s disease.

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Acknowledgements

The work in JP’s laboratory is supported by grants from NIH-NIA (1R21AG031429-01A2), Alzheimer’s Association (IIRG-08-90842), Small Research Pilot Grant from Signature Interdisciplinary Program in Neuroscience at University of South Florida, and startup funds from the Byrd Alzheimer’s Institute and Department of Molecular Medicine.

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  1. Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA

    Neha Kabra Woods & Jaya Padmanabhan Ph.D.

  2. Department of Molecular Medicine, USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, FL, 33613, USA

    Neha Kabra Woods & Jaya Padmanabhan Ph.D.

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  1. Neha Kabra Woods
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  2. Jaya Padmanabhan Ph.D.
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Correspondence to Jaya Padmanabhan Ph.D. .

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    Md. Shahidul Islam

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Woods, N.K., Padmanabhan, J. (2012). Neuronal Calcium Signaling and Alzheimer’s Disease. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 740. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2888-2_54

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