RT info:eu-repo/semantics/article
T1 Mitochondrial Ca2+ overload underlies Aβ oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs
A1 Sanz Blasco, Sara
A1 Valero, Ruth Ana
A1 Rodríguez Crespo, Ignacio
A1 Villalobos Jorge, Carlos
A1 Núñez Llorente, Lucía
K1 Calcium
K1 Calcio
K1 Amyloid-β oligomers
K1 Oligómeros β-amiloides
K1 Neurotoxicity
K1 Neurotoxicidad
K1 Neuroprotection
K1 Neuroprotección
AB Dysregulation of intracellular Ca2+ homeostasis may underlie amyloid β peptide (Aβ) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Aβ1–42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Aβ fibrils, induce a massive entry of Ca2+ in neurons and promote mitochondrial Ca2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Aβ oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca2+ overload, cytochrome c release and cell death induced by Aβ oligomers. Our results indicate that i) mitochondrial Ca2+ overload underlies the neurotoxicity induced by Aβ oligomers and ii) inhibition of mitochondrial Ca2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Aβ oligomers and AD.
PB Public Library of Science
SN 1932-6203
YR 2008
FD 2008
LK http://uvadoc.uva.es/handle/10324/45069
UL http://uvadoc.uva.es/handle/10324/45069
LA eng
NO PLoS ONE, 2008, vol. 3, n. 7. 16 p.
NO Producción Científica
DS UVaDOC
RD 11-jul-2024