Ibuprofen and lipoic acid conjugate neuroprotective activity is mediated by Ngb/Akt intracellular signaling pathway in Alzheimer's disease rat model. (Articolo in rivista)

Type
Label
  • Ibuprofen and lipoic acid conjugate neuroprotective activity is mediated by Ngb/Akt intracellular signaling pathway in Alzheimer's disease rat model. (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1159/000346445 (literal)
Alternative label
  • Zara S, De Colli M, Rapino M, Pacella S, Nasuti C, Sozio P, Di Stefano A, Cataldi A. (2013)
    Ibuprofen and lipoic acid conjugate neuroprotective activity is mediated by Ngb/Akt intracellular signaling pathway in Alzheimer's disease rat model.
    in Gerontology (Basel)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Zara S, De Colli M, Rapino M, Pacella S, Nasuti C, Sozio P, Di Stefano A, Cataldi A. (literal)
Pagina inizio
  • 250 (literal)
Pagina fine
  • 260 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 59 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 11 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Farmacia, Università 'G. d'Annunzio', Chieti, Italia Istituto di Genetica Molecolare del CNR, Unità di Chieti, Italia Dipartimento di Medicina e Scienze dell'Invecchiamento, Università 'G. d'Annunzio', Chieti, Italia Dipartimento di Medicina Sperimentale e Sanità Pubblica, Università di Camerino, Camerino, Italia (literal)
Titolo
  • Ibuprofen and lipoic acid conjugate neuroprotective activity is mediated by Ngb/Akt intracellular signaling pathway in Alzheimer's disease rat model. (literal)
Abstract
  • Background: Alzheimer's disease (AD) is a frequent form of senile dementia. Neuroglobin (Ngb) has a neuroprotective role and decreases A? peptide levels. Ngb, promoting Akt phosphorylation, activates cell survival involving cyclic-nucleotide response element-binding protein (CREB). A new molecule (IBU-LA) was synthetized and administered to an AD rat model to counteract AD progression. Objective: The aim of this study was to investigate the IBU-LA-mediated induction of Ngb neuroprotective and antiapoptotic activities. Methods: Brain morphology was analyzed through Bielschowsky staining, A?(1-40) and Ngb expression by immunohistochemistry. Akt, p-Akt, CREB and p-CREB expression was evaluated by Western blot, apoptosis through cytochrome C/Apaf 1 immunocomplex formation, and TUNEL analysis. Results: Bielschowsky staining and A?(1-40) expression show few nerve connections and A?(1-40) expression in an A? sample, preserved neuronal cells and A?(1-40) expression lowering in an IBU sample, mostly in IBU-LA. The Ngb level decreases in A? samples, compared to control and IBU-LA samples. p-Akt/Akt and p-CREB/CREB ratios reveal a reduction in A? sample, going back to the basal level in control and IBU-LA samples. Cytochrome C/Apaf 1 co-immunoprecipitate occurs and TUNEL-positive nuclei percentage decreases in A? sample. Probe test performance shows an increased spatial reference memory in the IBU-LA compared to the A? sample; no significant differences were seen between the IBU-LA and IBU samples. Conclusion: This evidence reveals that IBU-LA administration has the capability to maintain a high Ngb level allowing Ngb to perform a neuroprotective and antiapoptotic role, representing a valid tool in the therapeutic strategy of AD progression. (literal)
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