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Biochim Biophys Acta. 2015 Jul;1852(7):1465-76. doi: 10.1016/j.bbadis.2015.04.007. Epub 2015 Apr 16.

Inhibition of PMCA activity by tau as a function of aging and Alzheimer's neuropathology.

Author information

1
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain.
2
Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, 28049 Madrid, Spain.
3
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain. Electronic address: anam@unex.es.

Abstract

Ca2+-ATPases are plasma membrane and intracellular membrane transporters that use the energy of ATP hydrolysis to pump cytosolic Ca2+ out of the cell (PMCA) or into internal stores. These pumps are the main high-affinity Ca2+ systems involved in the maintenance of intracellular free Ca2+ at the properly low level in eukaryotic cells. The failure of neurons to keep optimal intracellular Ca2+ concentrations is a common feature of neurodegeneration by aging and aging-linked neuropathologies, such as Alzheimer's disease (AD). This disease is characterized by the accumulation of β-amyloid senile plaques and neurofibrillary tangles of tau, a protein that plays a key role in axonal transport. Here we show a novel inhibition of PMCA activity by tau which is concentration-dependent. The extent of inhibition significantly decreases with aging in mice and control human brain membranes, but inhibition profiles were similar in AD-affected brain membrane preparations, independently of age. No significant changes in PMCA expression and localization with aging or neuropathology were found. These results point out a link between Ca2+-transporters, aging and neurodegeneration mediated by tau protein.

KEYWORDS:

Aging; Alzheimer´s disease; Calcium; PMCA; Tau

PMID:
25892185
DOI:
10.1016/j.bbadis.2015.04.007
[Indexed for MEDLINE]
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