- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Nitric Oxide and Endothelin Effects
- Ion channel regulation and function
- Electron Spin Resonance Studies
- Neuropeptides and Animal Physiology
- Free Radicals and Antioxidants
- Nicotinic Acetylcholine Receptors Study
- Biochemical effects in animals
- Neurogenesis and neuroplasticity mechanisms
- Computational Drug Discovery Methods
- Chemical synthesis and alkaloids
- Genetics and Neurodevelopmental Disorders
- Molecular Sensors and Ion Detection
- Biochemical Analysis and Sensing Techniques
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Synthesis and biological activity
- Lipid Membrane Structure and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Synthesis of Organic Compounds
- GABA and Rice Research
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Sirtuins and Resveratrol in Medicine
Universidad Complutense de Madrid
2016-2025
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
2019-2025
Hospital Universitario Ramón y Cajal
2019
Consejo Superior de Investigaciones Científicas
1994-2006
Hôpital Saint-Louis
1994
Université Claude Bernard Lyon 1
1994
Centre National de la Recherche Scientifique
1989
Inserm
1989
Cadmium is an extremely toxic metal commonly found in industrial workplaces, a food contaminant and major component of cigarette smoke. can severely damage several organs, including the brain. In this work, we have studied both cadmium toxicity on rat cortical neurons culture possible protective effect serum. Our results indicate that: (1) taken up by dose serum dependent way; (2) cadmium, at concentrations from 1 μ M or 10 (depending absence presence serum) to 100 , decreases metabolic...
We report the synthesis, theoretical calculations, antioxidant, anti-inflammatory, and neuroprotective properties, ability to cross blood-brain barrier (BBB) of (Z)-α-aryl heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority compete with DMSO hydroxyl radicals, most them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that 1-3 10 give rise significant neuroprotection. When compounds 1-11 were tested necrotic cell...
We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. have identified compound 14n promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), moderate hAChE 1.73 0.34 μM), hMAO A 2.78 0.12 MAO B 21.29 3.85 μM) inhibition, while keeping a antioxidant power (3.04 TE, ORAC test). Consequently, results reported here support...
In this work, we have studied the effects of pure nitric oxide (NO) on regulation catecholamine (CA) secretion by chromaffin cells, as well possible presence its synthesizing enzyme L-arginine:NO synthase (NOS) in these cells. Our results show that NO produces a large stimulation basal CA secretion. This effect was calcium- and concentration-dependent (EC50 = 64 +/- 8 microM) not due to nonspecific damage tissue NO. also modulates evoked nicotine dose-dependent manner. Although it has...
Abstract Nitric oxide (NO) is an unstable molecule with physiological and pathological properties. In brain, NO acts as a modulator of neurotransmission well protector against neuronal death from several stimuli. However, beside this effect, high concentrations produce by mechanism in which the caspase pathway implicated. work, we demonstrate that cortical neurons toxicity mediated mitochondrial dysfunction. SNAP, donor, induces apoptosis these cells because it 1) increases p53 2) cytochrome...
The synthesis, toxicity, neuroprotection, and human acetylcholinesterase (hAChE)/ butyrylcholinesterase (hBuChE) inhibition properties of β-naphthotacrines1-14 as new drugs for Alzheimer's disease (AD) potential treatment, are reported. β-Naphthotacrines1-14 showed lower toxicity than tacrine; moreover, at the highest concentration assayed (300 μM) compounds 7, 10 11 displayed 2.25-2.01-fold higher cell viability tacrine in HepG2 cells. A neuroprotective effect was observed a neuronal...
The involvement of plasma membrane glutamate transporters (EAATs - excitatory aminoacid transporters) in the pathophysiology ischemia has been widely studied, but little is known about role vesicular (VGLUTs) ischemic process. We analyzed expression VGLUT1-3 cortex and caudate-putamen rats subjected to transient middle cerebral artery occlusion. Western blot immunohistochemistry revealed an increase VGLUT1 signal until 3 days reperfusion followed by a reduction 7 after insult. By contrast,...
This work relates to the design and synthesis of a series novel multi-target directed ligands (MTDLs), i.e., compounds 4a–l, via convenient one-pot three-component Hantzsch reaction. approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as promising compound, demonstrating robust activity, ability activate Nrf2-ARE pathways, well blockade inhibition. Dihydropyridine represents...
Histamine and the guanosine 3',5'-cyclic monophosphate (cGMP)-inducing agent sodium nitroprusside both increased serotonin (5-HT) uptake cGMP levels in isolated human platelets vitro. Histaminergic stimulation was observed at concentrations ranging from 10 nM to 0.25 microM [mean effective concentration (EC50) = 0.1 histamine]. The inhibition produced by H2-receptor antagonists tiotidine, metiamide, cimetidine 10-10(5) times more potent on histamine receptors regulating 5-HT generation than...
Previous work of our group stated that exogenously added and endogenous nitric oxide (NO) generated by cytokines induce apoptosis in chromaffin cells. In this work, we investigate the specific regulation NO synthase (NOS) isoforms, inducible NOS (iNOS) neuronal (nNOS), their particular participation cell death induced interferon gamma (IFNgamma). Lipopolysaccharide (LPS) IFNgamma increase iNOS expression, with no effect on nNOS expression. On other hand, dexamethasone increases basal...
Phytoestrogens can have a neuroprotective effect towards ischemia-reperfusion-induced neuronal damage. However, their mechanism of action has not been well described. In this work, we investigate the type cell death induced by oxygen and glucose deprivation (OGD) resupply (OGDR) pinpoint some signaling mechanisms whereby effects phytoestrogens occur in these conditions. First, found that autophagy initiation affords protection upon damage OGD OGDR. The mammalian target rapamycin/ribosomal S6...
Abstract GABA stimulates the basal catecholamine release from adrenal bovine chromaffin cells in a calciumdependent manner. This represents about 70% of that obtained by similar doses nicotine under experimental conditions. effect is mediated A receptor sites present cells, since it was mimicked muscimol and reversed bicuculline. In addition, GABA, through its receptors, increases evoked submaximal aicotine, but has no on nicotine‐evoked secretion catecholamines when given at maximal doses....
Abstract We herein report the synthesis, antioxidant power and neuroprotective properties of nine homo-bis-nitrones HBNs 1 – 9 as alpha-phenyl- N - tert -butylnitrone ( PBN ) analogues for stroke therapy. In vitro neuroprotection studies against Oligomycin A/Rotenone in an oxygen-glucose-deprivation model ischemia human neuroblastoma cell cultures, indicate that (1 Z ,1′ )-1,1′-(1,3-phenylene)bis( -benzylmethanimine oxide) HBN6 is a potent agent prevents decrease neuronal metabolic activity...