Browsing by Author "Brites, D."
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- A NOVEL DELETION IN UDP-GLUCURONOSYLTRANSFERASE GENE IN A PATIENT PRESENTING CRIGLER-NAJJAR SYNDROME TYPE IPublication . Elisio, C.; Vieira, E.; Lopes, A. I.; Saldanha, M. J.; Brites, D.; Dos Santos, R.
- Acetylcholinesterase inhibitory activity of oxazole derivativesPublication . Dias, Catarina; Brito, M. A.; Eleutério, A.; Marco, J. L.; Brites, D.; Carreiras, M. C.Alzheimer’s disease (AD) is the most common form of dementia among persons over 65 years of age. It is a brain neurodegenerative disorder characterised by loss of memory and cognition. Current treatment is symptomatic, with the major therapeutic strategy based on the “cholinergic hypothesis”, specifically acetylcholinesterase (AChE) inhibition. Tacrine (THA) was the first and one of the few drugs approved in the last decade for the treatment of AD. However, due to the important adverse effects, such as hepatotoxicity, it is no longer widely used. Therefore, more potent and less aggressive THA analogues are necessary. This prompted us to evaluate the AChE inhibitory activity of new oxazole derivatives (compounds 1-5), presenting a pyridine ring (compounds 2,3) or a benzene ring (compounds 4,5) in the molecule (1). The biological activity of the compounds was evaluated by measuring the AChE inhibitory activity by an adaptation of the method reported by Ellman et al (2). The reaction rates were compared and the percent of inhibition by the test compounds was calculated. Assays were performed in quadruplicate in at least two independent experiments, and THA was used as a reference compound. At the maximum soluble concentrations, compounds 1 and 2 inhibited AChE activity by nearly 50%, while the inhibition by the derivative 3 was only around 30%. In contrast, the oxazolo-derivatives 4 and 5 were devoid of any inhibitory activity, which we can speculate to be due to the absence of the N atom in the benzene ring in these compounds. Collectively, these preliminary findings point to a potential interest of precursor 1 and THA-derivative 2 for AD therapeutics, although structural modifications are needed to improve the solubility of the compounds, which is an essential step to enhance their activity. References: 1. Carreiras MC, Eleutério A, Marco-Contelles J, unpublished results. 2. Ellman, G. L. et al. Biochem. Pharmacol. 1961; 7: 88-95.
- ALTERATIONS IN NEURODEVELOPMENT OCCUR BY MODERATED LEVELS OF UNCONJUGATED BILIRUBIN AND INCREASE WHEN NEURONS ARE CO-CULTURED WITH ASTROCYTESPublication . Falcao, A.; Fernandes, A.; Silva, S. L.; Vaz, A. R.; Brito, M. A.; Henrique, D.; Silva, R. F.; Brites, D.
- BILIRUBIN-INDUCED CHANGES AT NEURONAL CYTOSKELETAL DYNAMICSPublication . Fernandes, A.; Coutinho, E.; Lanier, L. M.; Brites, D.
- Biological risks for neurological abnormalities associated with hyperbilirubinemiaPublication . Brites, D.; Fernandes, A.; Falcao, A. S.; Gordo, A. C.; Silva, R. F. M.; Brito, M. A.Unconjugated bilirubin (UCB) injury to glial cells leads to the secretion of glutamate and elicits a typical inflammatory response. Release of pro-inflammatory cytokines may influence gliogenesis and neurogenesis, and lead to deficits in learning and memo. - Fundacao para a Ciencia e a Tecnologia (FCT), Lisbon, Portugal. - The authors are grateful to the Fundacao para a Ciencia e a Tecnologia (FCT), Lisbon, Portugal, for their support.
- Exploring Multidrug resistance-associated Protein 1 (MRP1) expression during Neural Stem Cell Proliferation and Diferentiation, Nerve Cell Maturation and Neuro-Glia InteractionsPublication . Falcao, A.; Torrado, E.; Fernandes, A.; Abranches, E.; Bekman, E.; Brito, A.; Silva, R. F. M.; Henrique, D.; Brites, D.
- Implications of nitrosative stress in apoptotic cascades mediated by pro-inflammatory cytokines in immature neuronsPublication . Vaz, A. R.; Leitão Silva, S.; Barateiro, A.; Fernandes, A.; Falcão, A. S.; Silva, R. F. M.; Brito, M. A.; Brites, D.The inflammatory response is essential for survival in response to tissue injury or infection, but it can also cause neuronal damage [1]. In fact, pro-inflammatory cytokines, as well as nitric oxide (NO), are known as mediators of neuronal apoptosis [2,3]. Although apoptosis occurs physiologically in the brain during the period of the growth spurt, an increase in the number of neurons undergoing apoptosis may produce neuropathological sequelae [4]. Therefore, the aim of the present study was to: (i) deepen characterize the mechanisms of neuronal apoptosis upon cytokine exposure in neuronal immature cells; and (ii) investigate the role of NO as a determinant.
- Inhibition of nitric oxide production prevents apoptotic features mediated by inflammation in immature neuronsPublication . Vaz, A. R.; Silva, S. Leitao; Barateiro, A.; Fernandes, A.; Falcao, A. S.; Silva, R. F. M.; Brito, M. A.; Brites, D.
- Microglia acquires a phagocytic or pro-inflammatory phenotype when bilirubin gets into the brainPublication . Leitão Silva, S.; Osório, C.; Vaz, A. R.; Barateiro, A.; Falcão, A. S.; Brito, M. A.; Fernandes, A.; Silva, R. F. M.; Brites, D.
- Nitric Oxide mediates Inflammation-Induced Apoptotic Features and Neuronal Dysfunction at an early stage of NeurodevelopmentPublication . Vaz, A. R.; Silva, Leitao S.; Barateiro, A.; Falcao, A. S.; Fernandes, A.; Silva, R. F. M.; Brito, M. A.; Brites, D.