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dc.contributor.author
Sanz Blasco, Sara Isabel
dc.contributor.author
Calvo Rodriguez, Maria
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Caballero, Erica
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Garcia-Durillo, Monica
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Nunez, Lucia
dc.contributor.author
Villalobos, Carlos
dc.date.available
2018-06-04T17:42:50Z
dc.date.issued
2018-04
dc.identifier.citation
Sanz Blasco, Sara Isabel; Calvo Rodriguez, Maria; Caballero, Erica; Garcia-Durillo, Monica; Nunez, Lucia; et al.; Is it All Said for NSAIDs in Alzheimer's Disease? Role of Mitochondrial Calcium Uptake; Bentham Science Publishers; Current Alzheimer Research; 15; 6; 4-2018; 504-510
dc.identifier.issn
1567-2050
dc.identifier.uri
http://hdl.handle.net/11336/47161
dc.description.abstract
Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer´s disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing. Possible explanations include the view that NSAIDs and other possible disease-modifying drugs should be provided before the patients develop symptoms of AD or cognitive decline. In addition, NSAID targets for neuroprotection are unclear. Both COX-dependent and independent mechanisms have been proposed, including γ-secretase that cleaves the amyloid precursor protein (APP) and yields amyloid β peptide (Aβ). We have proposed a neuroprotection mechanism for NSAIDs based on inhibition of mitochondrial Ca2+ overload. Aβ oligomers promote Ca2+ influx and mitochondrial Ca2+ overload leading to neuron cell death. Several non-specific NSAIDs including ibuprofen, sulindac, indomethacin and R-flurbiprofen depolarize mitochondria in the low µM range and prevent mitochondrial Ca2+ overload induced by Aβ oligomers and/or N-methyl-D-aspartate (NMDA). However, at larger concentrations, NSAIDs may collapse mitochondrial potential (ΔΨ) leading to cell death. Accordingly, this mechanism may explain neuroprotection at low concentrations and damage at larger doses, thus providing clues on the failure of promising trials. Perhaps lower NSAID concentrations and/or alternative compounds with larger dynamic ranges should be considered for future trials to provide definitive evidence of neuroprotection against AD.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Bentham Science Publishers
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Alzheimer'S Disease
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Non-Steroidal Anti-Inflammatory Drugs
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Calcium
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Mitochondria
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Amyloid Β Oligomers
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N-Methyl-D-Aspartate
dc.subject.classification
Inmunología
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Is it All Said for NSAIDs in Alzheimer's Disease? Role of Mitochondrial Calcium Uptake
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-01T19:26:27Z
dc.journal.volume
15
dc.journal.number
6
dc.journal.pagination
504-510
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Oak Park
dc.description.fil
Fil: Sanz Blasco, Sara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Calvo Rodriguez, Maria. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Caballero, Erica. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Garcia-Durillo, Monica. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Nunez, Lucia. Consejo Superior de Investigaciones Científicas; España
dc.description.fil
Fil: Villalobos, Carlos. Consejo Superior de Investigaciones Científicas; España
dc.journal.title
Current Alzheimer Research
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.2174/1567205015666171227154016
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/158662/article
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