2026-05-05T18:29:06Zhttps://uvadoc.uva.es/oai/request
oai:uvadoc.uva.es:10324/450692021-06-24T07:16:57Zcom_10324_44585com_10324_954com_10324_894col_10324_44586
UVaDOC author Sanz Blasco, Sara author Valero, Ruth Ana author Rodríguez Crespo, Ignacio author Villalobos Jorge, Carlos author Núñez Llorente, Lucía 2021-01-19T09:51:33Z 2021-01-19T09:51:33Z 2008 PLoS ONE, 2008, vol. 3, n. 7. 16 p. 1932-6203 http://uvadoc.uva.es/handle/10324/45069 10.1371/journal.pone.0002718 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. eng Attribution-NonCommercial-NoDerivs 3.0 Unported Mitochondrial Ca2+ overload underlies Aβ oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs info:eu-repo/semantics/article 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URL https://uvadoc.uva.es/bitstream/10324/45069/1/Mitochondrial-Ca2-overload.pdf File MD5 7c98b9480b1f3e61ece975d61218fe97 924366 application/pdf Mitochondrial-Ca2-overload.pdf