Calcium and neurodegeneration
By Mark P. Mattson. Aging Cell, 2007
760 citations recorded by the source corpus.
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 β‐peptide, α‐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, α‐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.
Subfields: Cellular and Molecular Neuroscience, Neurology, Physiology
View Paper: https://www.semanticscholar.org/paper/5fdda5bc60c653cc10f28a49e6e9aa206aa22304
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In Cellular and Molecular Neuroscience
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Citations in the corpus
- Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “Excessive ER stress and dysregulation of ER Ca 2 þ homeostasis is believed to contribute to the dysfunction and death of neurons in ischemic stroke (412), AD (32, 283, 290), and Parkinson’s disease (233).”
- Oxidative stress, mitochondrial damage and neurodegenerative diseases (2013, background): “In fact, genetic and pharmacological manipulations that enhance mitochondrial Ca 2+ sequestration can protect neurons against excitotoxicity [30] .”
- Aβ Oligomers Cause Localized Ca2+ Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines (2010, background): “, proteasome, mitochondria) and perturbation of calcium homeostasis (Mattson, 2007).”
- PINK1-Associated Parkinson's Disease Is Caused by Neuronal Vulnerability to Calcium-Induced Cell Death (2009, background): “, 2003, 2004), Huntington’s disease, amyotrophic lateral sclerosis, and stroke (Mattson, 2007).”
- Hallmarks of neurodegenerative diseases. (2023, neutral): “Synaptic function in turn is modulated by neurotransmitter 91–93 and calcium changes, 91,93,94 cytoskeletal adaptations, 95 presynaptic vesicle dynamics, and post-synaptic signaling 91–93 , 96 (Figure 3).”