Ibuprofen and lipoic acid conjugate neuroprotective activity is mediated by Ngb/Akt intracellular signaling pathway in Alzheimer's disease rat model.
Gerontology
; 59(3): 250-60, 2013.
Article
en En
| MEDLINE
| ID: mdl-23428737
BACKGROUND: Alzheimer's disease (AD) is a frequent form of senile dementia. Neuroglobin (Ngb) has a neuroprotective role and decreases Aß 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, Aß(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 Aß(1-40) expression show few nerve connections and Aß(1-40) expression in an Aß sample, preserved neuronal cells and Aß(1-40) expression lowering in an IBU sample, mostly in IBU-LA. The Ngb level decreases in Aß samples, compared to control and IBU-LA samples. p-Akt/Akt and p-CREB/CREB ratios reveal a reduction in Aß 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 Aß sample. Probe test performance shows an increased spatial reference memory in the IBU-LA compared to the Aß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Globinas
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Ibuprofeno
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Fármacos Neuroprotectores
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Proteínas Proto-Oncogénicas c-akt
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Enfermedad de Alzheimer
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Proteínas del Tejido Nervioso
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Gerontology
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Suiza