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

© 2015 Elsevier B.V.. Ca<sup>2+</sup>-ATPases are plasma membrane and intracellular membrane transporters that use the energy of ATP hydrolysis to pump cytosolic Ca<sup>2+</sup> out of the cell (PMCA) or into internal stores. These pumps are the main high-affinity Ca<sup&g...

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Detalles Bibliográficos
Autores: Berrocal, María, Corbacho, Isaac, Vázquez-Hernández, María, Ávila, Jesús, Sepúlveda, M. Rosario, Mata, Ana M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/139543
Acceso en línea:http://hdl.handle.net/10261/139543
Access Level:acceso abierto
Palabra clave:PMCA
Tau
Calcium
Aging
Alzheimer disease
Descripción
Sumario:© 2015 Elsevier B.V.. Ca<sup>2+</sup>-ATPases are plasma membrane and intracellular membrane transporters that use the energy of ATP hydrolysis to pump cytosolic Ca<sup>2+</sup> out of the cell (PMCA) or into internal stores. These pumps are the main high-affinity Ca<sup>2+</sup> systems involved in the maintenance of intracellular free Ca<sup>2+</sup> at the properly low level in eukaryotic cells. The failure of neurons to keep optimal intracellular Ca<sup>2+</sup> 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 Ca<sup>2+</sup>-transporters, aging and neurodegeneration mediated by tau protein.