A5046358279- Cholinesterase and Neurodegenerative Diseases
- Nicotinic Acetylcholine Receptors Study
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Inflammasome and immune disorders
- Tryptophan and brain disorders
- Genomics, phytochemicals, and oxidative stress
- Heme Oxygenase-1 and Carbon Monoxide
- S100 Proteins and Annexins
- Alzheimer's disease research and treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Comparative Literary Analysis and Criticism
- Adenosine and Purinergic Signaling
- Traumatic Brain Injury and Neurovascular Disturbances
- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Nitric Oxide and Endothelin Effects
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Chemical synthesis and alkaloids
- ATP Synthase and ATPases Research
- Neuroscience of respiration and sleep
- Vagus Nerve Stimulation Research
Hospital Universitario Santa Cristina
2018-2025
Hospital Universitario de La Princesa
2014-2025
Universidad Autónoma de Madrid
2014-2023
Hospital Universitario Virgen del Rocío
2017
Hospital La Paz Institute for Health Research
2010-2011
Hospital Universitario La Paz
2010-2011
Zero to Three
2010
Acute kidney injury is a common complication of rhabdomyolysis. A better understanding this syndrome may be useful to identify novel therapeutic targets because there no specific treatment so far. Ferroptosis an iron-dependent form regulated nonapoptotic cell death that involved in renal injury. In study, we investigated whether ferroptosis associated with rhabdomyolysis-mediated damage, and studied the effect curcumin, powerful antioxidant renoprotective properties. Induction rhabdomyolysis...
Significance Current one drug–one target–one disease approaches in drug discovery have become increasingly inefficient. Network pharmacology defines mechanisms as networks best targeted by multiple, synergistic drugs. Using the high unmet medical need indication stroke, we here develop an integrative silico approach based on a primary target, NADPH oxidase type 4, to identify mechanistically related cotarget, NO synthase, for network pharmacology. Indeed, validate both vivo and vitro,...
We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving activation nuclear factor erythroid-2-related 2 (Nrf2) and/or expression its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, protective pharmacologic alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) vitro as well...
Significance Why the brain is uniquely sensitive to hypoxia and which cells are involved incompletely understood. Here we identify that, upon ischemic stroke, in endothelial neurons reactive oxygen-forming NADPH oxidase 4 (NOX4) causes breakdown of BBB neuronal cell death. This mechanism unique not found other forms ischemia body. Genetic deletion either type (endothelial or neuronal) pharmacological inhibition NOX4 leads a significant reduction infarct volume direct neuroprotection....
Twenty-six new tacrine–benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most exhibited good inhibitory activities cholinesterases β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed most interesting profile as a subnanomolar selective inhibitor acetylcholinesterase (hAChE) (IC50 = 0.86 nM) both aggregation (hAChE- self-induced,...
Mitochondria use oxygen as the final acceptor of respiratory chain, but its incomplete reduction can also produce reactive species (ROS), especially superoxide. Acute hypoxia produces a superoxide burst in different cell types, triggering mechanism is still unknown. Herein, we show that complex I involved this under acute endothelial cells. We have studied possible mechanisms by which could be burst, discarding reverse electron transport and implication PTEN-induced putative kinase 1...
Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order modulate oxidative stress as therapeutic strategy. Compound 5c has been identified promising permeable agent showing excellent properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, best neuroprotective capacity, being...
Abstract The therapy of complex neurodegenerative diseases requires the development multitarget‐directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well histamine H 3 receptor (H3R) were obtained by optimization neuroprotectant ASS234 incorporating generally accepted H3R pharmacophore motifs. These small‐molecule hits demonstrated balanced activities at targets, mostly in nanomolar concentration range....
Ischemic stroke is a predominant cause of disability worldwide, with thrombolytic or mechanical removal the occlusion being only therapeutic option. Reperfusion bears risk an acute deleterious calcium-dependent breakdown blood-brain barrier. Its mechanism, however, unknown. Here, we identified type 5 NADPH oxidase (NOX5), calcium-activated, ROS-forming enzyme, as missing link. Using humanized knockin (KI) mouse model and in vitro organotypic cultures, found that reoxygenation calcium...
Activation of astrocytes contributes to synaptic remodelling, tissue repair and neuronal survival following traumatic brain injury (TBI). The mechanisms by which these cells interact resident/infiltrated inflammatory rewire networks functions remain poorly understood. Here, we explored how TLR4-induced astrocyte activation modified synapses cerebrovascular integrity TBI.To determine functional alterations induced TLR4 pathway in regulate neurovascular after TBI, used pharmacology, genetic...
Mitochondrial perturbation and oxidative stress are key factors in neuronal vulnerability several neurodegenerative diseases or during brain ischemia. Here we have investigated the protective mechanism of action guanosine, guanine nucleoside, a human neuroblastoma cell line, SH-SY5Y, subjected to mitochondrial stress. Blockade complexes I V with rotenone plus oligomycin (Rot/oligo) caused significant decrease viability an increase ROS production. Guanosine that effect guanosine incubated...
Abstract The mechanism of the neuroprotective action tetracycline antibiotic minocycline against various neuron insults is controversial. In an attempt to clarify this mechanism, we have studied here its effects on electrophysiological parameters, Ca 2+ signalling, and glutamate release, in primary cultures rat hippocampal neurons, synaptosomes. Spontaneous excitatory postsynaptic currents potential firing were drastically decreased by at concentrations known afford neuroprotection. drug...
Melatonin has been widely studied as a protective agent against oxidative stress. However, the molecular mechanisms underlying neuroprotection in neurodegeneration and ischemic stroke are not yet well understood. In this study, we evaluated neuroprotective/antioxidant mechanism of action melatonin organotypic hippocampal cultures (OHCs) photothrombotic model vivo. (0.1, 1, 10 μM) incubated postoxygen glucose deprivation (OGD) showed concentration-dependent protection; maximum protection was...
Guanosine (GUO) is an endogenous modulator of glutamatergic excitotoxicity and has been shown to promote neuroprotection in vivo vitro models neurotoxicity. This study was designed understand the neuroprotective mechanism GUO against oxidative damage promoted by oxygen/glucose deprivation reoxygenation (OGD). (100 μM) reduced reactive oxygen species production prevented mitochondrial membrane depolarization induced OGD. also exhibited anti-inflammatory actions as inhibition nuclear factor...