Searching for a role of NCX/NCKX exchangers in neurodegeneration.
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 beta-amyloid toxicity. In this review, we summarize the current knowledge about the Na+/Ca2+ exchanger families and their implications in neurodegenerative disorders.
Gomez-Villafuertes
Rosa
R
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Mellström
Britt
B
Naranjo
Jose R
JR
D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D020033:Protein Isoforms; D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger