María Delgado-Esteban

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Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that destabilizes cell cycle proteins, is activated by Cdh1 in post-mitotic neurons, where it regulates axonal growth, synaptic plasticity and survival. The APC/C-Cdh1 substrate, cyclin B1, has been found to accumulate in degenerating brain areas in Alzheimer's disease and stroke. This(More)
Oxidative damage has been reported to be involved in the pathogenesis of diabetic neuropathy and neurodegenerative diseases. Recent evidence suggests that the antidiabetic drug metformin prevents oxidative stress-related cellular death in non-neuronal cell lines. In this report, we point to the direct neuroprotective effect of metformin, using the(More)
In order to investigate the potential neuroprotective role played by glucose metabolism during brain oxygen deprivation, the susceptibility of cultured neurones and astrocytes to 1 h of oxygen deprivation (hypoxia) or oxygen and glucose deprivation (OGD) was examined. OGD, but not hypoxia, promotes dihydrorhodamine 123 and glutathione oxidation in neurones(More)
Besides its essential role at regulating neural functions through cyclic GMP, nitric oxide is emerging as an endogenous physiological modulator of energy conservation for the brain. Thus, nitric oxide inhibits cytochrome c oxidase activity in neurones and glia, resulting in down-regulation of mitochondrial energy production. The subsequent increase in AMP(More)
The possible neuroprotective effect of D-glucose against glutamate-mediated neurotoxicity was studied in rat cortical neurons in primary culture. Brief (5-min) exposure of neurons to glutamate (100 microM) increased delayed (24-h) necrosis and apoptosis by 3- and 1.8-fold, respectively. Glutamate-mediated neurotoxicity was accompanied by a(More)
High levels of unconjugated bilirubin (UCB) may initiate encephalopathy in neonatal life, mainly in pre-mature infants. The molecular mechanisms of this bilirubin-induced neurologic dysfunction (BIND) are not yet clarified and no neuroprotective strategy is currently worldwide accepted. Here, we show that UCB, at conditions mimicking those of(More)
Peroxynitrite is usually considered as a neurotoxic nitric oxide-derivative. However, an increasing body of evidence suggests that, at low concentrations, peroxynitrite affords transient cytoprotection, both in vitro and in vivo. Here, we addressed the signaling mechanism responsible for this effect, and found that rat cortical neurons in primary culture(More)
Following brain inflammatory stimuli, astrocytes actively synthesize nitric oxide and peroxynitrite. These nitrogen-derived species trigger a repertoire of biochemical effects, including alteration of mitochondrial function and redox status both in astrocytes and neighboring neurons. Furthermore, under such nitrosative stress astrocytes show remarkable(More)
The functional outcome after stroke is unpredictable; it is not accurately predicted by clinical pictures upon hospital admission. The presence of apoptotic neurons in the ischemic penumbra and perihematoma area may account for poor prognosis, but whether the highly variable stroke outcome reflects differences in genetic susceptibility to apoptosis is(More)
The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1--which regulates mitosis exit and G1-phase length in dividing cells--regulates neurogenesis in vivo.(More)