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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Article

Berrocal, Maria¹  Corbacho, Isaac¹  Vazquez-Hernandez, Maria^1,2  Avila, Jesus²  Rosario Sepulveda, M.¹  Mata, Ana M.¹ 

[1] Univ Extremadura, Fac Ciencias, Dept Bioquim & Biol Mol & Genet, Badajoz 06006, Spain

[2] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, Consejo Super Invest Cient, E-28049 Madrid, Spain

关键词: Tau;    Calcium;    PMCA;    Aging;    Alzheimer's disease;   

DOI  :  10.1016/j.bbadis.2015.04.007

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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