A5006586236- PI3K/AKT/mTOR signaling in cancer
- Neurological Disease Mechanisms and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Biochemical effects in animals
- Neurological Disorders and Treatments
- S100 Proteins and Annexins
- Nutritional Studies and Diet
- Calpain Protease Function and Regulation
- Receptor Mechanisms and Signaling
- Electron Spin Resonance Studies
- Autism Spectrum Disorder Research
- Cholesterol and Lipid Metabolism
- Diet and metabolism studies
- Neuroscience and Neuropharmacology Research
- Circadian rhythm and melatonin
- Free Radicals and Antioxidants
- Neuroinflammation and Neurodegeneration Mechanisms
- Acute Ischemic Stroke Management
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Fatty Acid Research and Health
- Dye analysis and toxicity
- Nerve injury and regeneration
- Biochemical Analysis and Sensing Techniques
- Polyamine Metabolism and Applications
Instituto de Biomedicina de Sevilla
2015-2024
Junta de Andalucía
2024
Spanish Clinical Research Network
2024
Instituto de Salud Carlos III
2023-2024
Centro de Investigación Biomédica en Red de Salud Mental
2023-2024
Hospital Universitario Virgen del Rocío
2015-2023
Universidad de Sevilla
2017-2023
Vall d'Hebron Institut de Recerca
2017
Universitat Autònoma de Barcelona
2017
Instituto Ramón y Cajal de Investigación Sanitaria
2011-2017
Since Toll-like receptor 4 (TLR4) mediates brain damage after stroke, development of TLR4 antagonists is a promising therapeutic strategy for this disease. Our aim was to generate TLR4-blocking DNA aptamers be used stroke treatment. From random oligonucleotide pool, we identified two (ApTLR#1R, ApTLR#4F) with high affinity human by systematic evolution ligands exponential enrichment (SELEX). Optimized truncated forms (ApTLR#1RT, ApTLR#4FT) were obtained. data demonstrate specific binding...
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 synthesis and neuroprotective capacity of an array 31 compounds comprising quinolyloximes, quinolylhydrazones, quinolylimines, QNs, related heterocyclic azolylnitrones. Neuronal cultures subjected to oxygen-glucose deprivation (OGD), as experimental model for ischemic conditions, were treated with our molecules at onset recovery period after OGD showed that most these but not azo molecules, improved neuronal viability 24 h recovery. Especially, QN ( Z)-...
Stroke is one of the leading causes death worldwide and while there increasing evidence that a Mediterranean diet might decrease risk stroke, effects dietary fat composition on stroke outcomes have not been fully explored. We hypothesize brain damage provoked by would be different depending source fat. To test this, male C57BL/6J mice were fed for 4 weeks with standard low-fat (LFD), high-fat (HFD) rich in saturated fatty acids (HFD-SFA), an HFD containing monounsaturated (MUFAs) from olive...
Eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) is a translational repressor that characterized by its capacity to bind specifically eIF4E and inhibit interaction with eIF4G. Phosphorylation of 4E-BP1 regulates availability, therefore, cap-dependent translation, in cell stress. This study reports physiological regulation phosphorylation using control conditions stress-induced repression condition, ischemia-reperfusion (IR) stress, brain tissue. In conditions, was found four...
This study describes CholesteroNitrone 2 as an antioxidant and neuroprotective agent against ischemic injury. Neuroprotection was assessed using in vitro vivo experimental ischemia models. The compound significantly increased cell viability, induced neuroprotection following reperfusion, decreased neurological deficit scores treated animals, supporting the next preclinical studies a potential for treatment of stroke.
There is a need to develop additional effective therapies for ischemic stroke. Nitrones, which were first developed as reactive oxygen species (ROS)-trapping compounds, have been proposed neuroprotective agents stroke, ROS-related disorder. The previous reported ROS-trapping compound, quinolyl nitrone RP19, here being assayed induce neuroprotection ischemia-reperfusion injury in three experimental ischemia models: (i) oxygen-glucose deprivation (OGD) on primary neuronal cultures; (ii)...
Finding an efficient neuroprotectant is of urgent need in the field stroke research. The goal this study was to test effect acute simvastatin administration after a rat embolic model and explore its mechanism action through brain proteomics. To that end, male Wistar rats were subjected Middle Cerebral Arteria Occlusion (20 mg/kg s.c) (n = 11) or vehicle 9) administered 15 min after. evaluate neuroprotective mechanisms simvastatin, homogenates 48 h analyzed by two-dimensional fluorescence...
Transient brain ischemia induces an inhibition of translational rates and causes delayed neuronal death in selective regions cognitive deficits, whereas these effects do not occur resistant areas. The repressor eukaryotic initiation factor (elF) 4E-binding protein-2 (4E-BP2) specifically binds to eIF4E is critical the control protein synthesis. To link translation inhibition, we study association with 4E-BP2 under reperfusion a rat model transient forebrain ischemia. Upon reperfusion,...
Stress granules (SGs) are cytoplasmic ribonucleoprotein aggregates that directly connected with the translation initiation arrest response to cellular stresses. Translation inhibition (TI) is observed in transient brain ischemia, a condition induces persistent TI even after reperfusion, i.e. when blood flow restored, and causes delayed neuronal death (DND) selective vulnerable regions. We previously described connection between DND hippocampal cornu ammonis 1 (CA1) an animal model of...
Abstract Several studies show great heterogeneity in the type of genetic test requested and clinicopathological characteristics patients with ASD. The following study aims, firstly, to explore factors that might influence professionals’ decisions about appropriateness requesting testing for their ASD and, secondly, determine prevalence alterations a representative sample children diagnosis Methods: We studied clinical associated request 440 present alterations. Even though main guidelines...
Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains major cause of neonatal mortality morbidity worldwide. Therapeutic hypothermia current standard care but it does not provide complete neuroprotection. Our aim was investigate neuroprotective effect oleuropein (Ole) in (seven-day-old) mouse model HI. Ole, secoiridoid found olive leaves, has previously shown reduce damage against cerebral other ischemia/reperfusion injuries....
Abstract Phosphorylation of the α subunit eukaryotic translation initiation factor 2 (eIF2α), which is one substrates protein phosphatase 1 (PP1), occurs rapidly during first minutes post‐ischemic reperfusion after an episode cerebral ischemia. In present work, two experimental models transient global ischemia and ischemic tolerance (IT) were used to study PP1 interacting/regulatory proteins following reperfusion. For that purpose we utilized purified by microcystin chromatography, as well...
Stroke is a disease of ageing affecting millions people worldwide, and recombinant tissue-type plasminogen activator (r-tPA) the only treatment approved. However, r-tPA has low therapeutic window secondary effects which limit its beneficial outcome, urging thus search for new more efficient therapies. Among them, neuroprotection based on melatonin or nitrones, as free radical traps, have arisen drug candidates due to their strong antioxidant power. In this Perspective, an update specific...
Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which two important issues in hypoxia-induced oxidative stress cell death brain ischemia. Consequently, nitrones been proposed therapeutic agents acute ischemic stroke (AIS). In this paper, we update the biological pharmacological characterization of ISQ-201, previously identified cholesteronitrone hybrid with antioxidant neuroprotective activity. This study characterizes ISQ-201 agent...
Eukaryotic initiation factor (eIF) 4E-binding proteins (4E-BPs) are translational repressors that bind specifically to eIF4E and critical in the control of protein translation. 4E-BP2 is predominant 4E-BP expressed brain, but their role not well known. Here, we characterized four forms detected by two-dimensional gel electrophoresis (2-DGE) brain. The form with highest electrophoretic mobility was main susceptible phosphorylation at Thr37/Thr46 sites, acidic spots. Cerebral ischemia...