Abstract
Perturbed neuronal calcium homeostasis is a prominent feature in Alzheimer's disease (AD). Mitochondria accumulate calcium ions (Ca(2+)) for cellular bioenergetic metabolism and suppression of mitochondrial motility within the cell. Excessive Ca(2+) uptake into mitochondria often leads to mitochondrial membrane permeabilization and induction of apoptosis. Ca(2+) is an interesting second messenger which can initiate both cellular life and death pathways in mitochondria. This review critically discusses the potential of manipulating mitochondrial Ca(2+) concentrations as a novel therapeutic opportunity for treating AD. This review also highlights the neuroprotective role of a number of currently available agents that modulate different mitochondrial Ca(2+) transport pathways. It is reasoned that these mitochondrial Ca(2+) modulators are most effective in combination with agents that increase the Ca(2+) buffering capacity of mitochondria. Modulation of mitochondrial Ca(2+) handling is a potential pharmacological target for future development of AD treatments.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / metabolism*
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Alzheimer Disease / physiopathology
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Alzheimer Disease / therapy*
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Animals
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Calcium Channel Blockers / pharmacology
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Calcium Channel Blockers / therapeutic use
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Calcium Signaling / drug effects*
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Calcium Signaling / physiology
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Calcium* / physiology
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Cell Death / drug effects
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Cell Death / physiology
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Cholinesterase Inhibitors / pharmacology
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Cholinesterase Inhibitors / therapeutic use
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Humans
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Mice
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Mitochondria / drug effects*
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Mitochondria / physiology
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Mitochondria / ultrastructure
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Mitochondrial Membranes / drug effects*
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Mitochondrial Membranes / physiology
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Molecular Targeted Therapy
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use
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Rats
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Submitochondrial Particles / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Calcium Channel Blockers
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Cholinesterase Inhibitors
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Neuroprotective Agents
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Receptors, N-Methyl-D-Aspartate
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Calcium