期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1852, 期 7, 页码 1465-1476出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2015.04.007
关键词
Tau; Calcium; PMCA; Aging; Alzheimer's disease
资金
- Ministerio de Economia y Competitividad [BFU2011-23313]
- Fundacion Marcelino Botin
- Junta de Extremadura
- FEDER
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 ofp-amyloid senile plagues 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. (C) 2015 Elsevier B.V. All rights reserved.
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