Neuronal calcium homeostasis and dysregulation.
The calcium ion (Ca(2+)) is the main second messenger that helps to transmit depolarization status and synaptic activity to the biochemical machinery of a neuron. These features make Ca(2+) regulation a critical process in neurons, which have developed extensive and intricate Ca(2+) signaling pathways. High intensity Ca(2+) signaling necessitates high ATP consumption to restore basal (low) intracellular Ca(2+) levels after Ca(2+) influx through plasma membrane receptor and voltage-dependent ion channels. Ca(2+) influx may also lead to increased generation of mitochondrial reactive oxygen species (ROS). Impaired abilities of neurons to maintain cellular energy levels and to suppress ROS may impact Ca(2+) signaling during aging and in neurodegenerative disease processes. This review focuses on mitochondrial and endoplasmic reticulum Ca(2+) homeostasis and how they relate to synaptic Ca(2+) signaling processes, neuronal energy metabolism, and ROS generation. Also, the contribution of altered Ca(2+) signaling to neurodegeneration during aging will be considered. Advances in understanding the molecular regulation of Ca(2+) homeostasis and how it is perturbed in neurological disorders may lead to therapeutic strategies that modulate neuronal Ca(2+) signaling to enhance function and counteract disease processes.
Gleichmann
Marc
M
Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland, USA. marc.gleichmann@gmail.com
Mattson
Mark P
MP
D000375:Aging / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological
D053496:Inositol 1,4,5-Trisphosphate Receptors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D053829:Amyloid Precursor Protein Secretases; D002118:Calcium