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Aging Cell. 2007 Jun;6(3):337-50. Epub 2007 Feb 28.

Calcium and neurodegeneration.

Author information

1
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA. mattsonm@grc.nia.nih.gov

Abstract

When properly controlled, Ca2+ fluxes across the plasma membrane and between intracellular compartments play critical roles in fundamental functions of neurons, including the regulation of neurite outgrowth and synaptogenesis, synaptic transmission and plasticity, and cell survival. During aging, and particularly in neurodegenerative disorders, cellular Ca2+-regulating systems are compromised resulting in synaptic dysfunction, impaired plasticity and neuronal degeneration. Oxidative stress, perturbed energy metabolism and aggregation of disease-related proteins (amyloid beta-peptide, alpha-synuclein, huntingtin, etc.) adversely affect Ca2+ homeostasis by mechanisms that have been elucidated recently. Alterations of Ca2+-regulating proteins in the plasma membrane (ligand- and voltage-gated Ca2+ channels, ion-motive ATPases, and glucose and glutamate transporters), endoplasmic reticulum (presenilin-1, Herp, and ryanodine and inositol triphosphate receptors), and mitochondria (electron transport chain proteins, Bcl-2 family members, and uncoupling proteins) are implicated in age-related neuronal dysfunction and disease. The adverse effects of aging on neuronal Ca2+ regulation are subject to modification by genetic (mutations in presenilins, alpha-synuclein, huntingtin, or Cu/Zn-superoxide dismutase; apolipoprotein E isotype, etc.) and environmental (dietary energy intake, exercise, exposure to toxins, etc.) factors that may cause or affect the risk of neurodegenerative disease. A better understanding of the cellular and molecular mechanisms that promote or prevent disturbances in cellular Ca2+ homeostasis during aging may lead to novel approaches for therapeutic intervention in neurological disorders such as Alzheimer's and Parkinson's diseases and stroke.

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