Ibuprofen and Lipoic Acid Conjugate Neuroprotective Activity Is Mediated by Ngb/Akt Intracellular Signaling Pathway in Alzheimer's Disease Rat Model

Background: Alzheimer's disease (AD) is a frequent form of senile dementia. Neuroglobin (Ngb) has a neuroprotective role and decreases A beta 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 beta(1-40) and Ngb expression by immunohistochennistry. Akt, p-Akt, CREB and p-CREB expression was evaluated by Western blot, apoptosis through cytochrome C/Apaf 1 innmunocomplex formation, and TUNEL analysis. Results: Bielschowsky staining and A beta(1-40) expression show few nerve connections and A beta(1-40) expression in an A beta sample, preserved neuronal cells and A beta(1-40) expression lowering in an IBU sample, mostly in IBU-LA. The Ngb level decreases in A beta samples, compared to control and IBU-LA samples. p-Akt/Akt and p-CREB/CREB ratios reveal a reduction in A beta 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 beta sample. Probe test performance shows an increased spatial reference memory in the IBU-LA compared to the A beta 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. Copyright (C) 2013 S. Karger AG, Basel