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Searching for a Role of NCX/NCKX Exchangers in Neurodegeneration

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Abstract

Control of intracellular calcium signaling is essential for neuronal development and function. Maintenance of Ca2+ homeostasis depends on the functioning of specific transport systems that remove calcium from the cytosol. Na+/Ca2+ exchange is the main calcium export mechanism across the plasma membrane that restores resting levels of calcium in neurons after stimulation. Two families of Na+/Ca2+ exchangers exist, one of which requires the co-transport of K+ and Ca2+ in exchange for Na+ ions. The malfunctioning of Na+/Ca2+ exchangers has been related to the development of pathological conditions in the regulation of neuronal death after hypoxia–anoxia, brain trauma, and nerve injury. In addition, the Na+/Ca2+ exchanger function has been associated with impaired Ca2+ homeostasis during aging of the brain, as well as with a role in Alzheimer’s disease by regulating β-amyloid toxicity. In this review, we summarize the current knowledge about the Na+/Ca2+ exchanger families and their implications in neurodegenerative disorders.

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Acknowledgment

This work was supported by grants from MEC, CAM, and FISS to J.R.N. and B.M. R.G.V. is recipient of a Juan de la Cierva contract (MEC).

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Correspondence to Jose R. Naranjo.

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Gomez-Villafuertes, R., Mellström, B. & Naranjo, J.R. Searching for a Role of NCX/NCKX Exchangers in Neurodegeneration. Mol Neurobiol 35, 195–202 (2007). https://doi.org/10.1007/s12035-007-0007-0

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Keywords

  • Calcium homeostasis
  • Ischemia
  • Alzheimer disease
  • Spinal cord injury
  • DREAM