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...
| Autores: | , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositório: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/139543 |
| Acesso em linha: | http://hdl.handle.net/10261/139543 |
| Access Level: | Acceso aberto |
| Palavra-chave: | PMCA Tau Calcium Aging Alzheimer disease |
| Resumo: | © 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. |
|---|