A5014815709- Adenosine and Purinergic Signaling
- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Neuroscience and Neuropharmacology Research
- Neurological Complications and Syndromes
- Biochemical and Molecular Research
- Alkaline Phosphatase Research Studies
- Pharmacological Effects and Toxicity Studies
- Adolescent and Pediatric Healthcare
- Tryptophan and brain disorders
- Drug Transport and Resistance Mechanisms
- Alzheimer's disease research and treatments
- MicroRNA in disease regulation
- Toxoplasma gondii Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Ubiquitin and proteasome pathways
- Parkinson's Disease Mechanisms and Treatments
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Neuroscience of respiration and sleep
- RNA Research and Splicing
- Retinal Development and Disorders
- Endoplasmic Reticulum Stress and Disease
- Restless Legs Syndrome Research
- Retinal Diseases and Treatments
Universidad Complutense de Madrid
2014-2025
Royal College of Surgeons in Ireland
2019-2023
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
2014-2020
Neuromod (Ireland)
2019
The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown be increased in the brain, including both microglia neurons, experimental models of epilepsy patients. To date, cell type-specific downstream effects P2X7Rs during seizures remain, however, incompletely understood.
Alzheimer disease is a neurodegenerative characterized by the presence of senile plaques composed amyloid-β (Aβ) peptide, neurofibrillary tangles, neuronal loss and neuroinflammation. Previous works have revealed that extracellular ATP, through its selective receptor P2X7 (P2X7R), essential to neuroinflammation neurotoxicity induced Aβ. P2X7R upregulated on microglial cells around plaques. This upregulation progressively rises with age parallel an accumulation also correlates synaptic...
Hypomorphic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNAP) enzyme, ALPL human or Akp2 mice, cause hypophosphatasia (HPP), an inherited metabolic bone disease also characterized by spontaneous seizures. Initially, these seizures were attributed to impairment of GABAergic neurotransmission caused altered vitamin B6 (vit-B6) metabolism. However, clinical cases newborns and adults whose convulsions are refractory pro-GABAergic drugs but controlled vit-B6...
There is a major unmet need for molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to-use point-of-care device. Purines such as adenosine triphosphate and are potent neuromodulators released during excessive neuronal activity also present biofluids. Their potential peripheral blood has, however, not yet been investigated. The aim the study was determine whether purine nucleoside measurements can serve recent occurrence support diagnosis...
Abstract Objective Pharmacoresistance and the lack of disease‐modifying actions current antiseizure drugs persist as major challenges in treatment epilepsy. Experimental models chemoconvulsant‐induced status epilepticus remain choice to discover potential antiepileptogenic drugs, but doubts extent which they model human pathophysiology. The aim present study was compare molecular landscape intra‐amygdala kainic acid mice with findings resected brain tissue from patients drug‐resistant...
Background and Purpose Refractory status epilepticus is a clinical emergency associated with high mortality morbidity. Increasing evidence suggests neuroinflammation contributes to the development of drug‐refractoriness during epilepticus. Here, we have determined contribution ATP‐gated P2X7 receptor, previously linked inflammation increased hyperexcitability, drug‐refractory its therapeutic potential. Experimental Approach Status was induced via unilateral microinjection kainic acid into...
Abstract Temporal lobe epilepsy is the most common and refractory form of in adults. Gene expression within affected structures such as hippocampus displays extensive dysregulation implicated a central pathomechanism. Post-transcriptional mechanisms are increasingly recognized determinants gene landscape, but key remain unexplored. Here we show, for first time, that cytoplasmic mRNA polyadenylation, one post-transcriptional regulating expression, undergoes widespread reorganization temporal...
Hypophosphatasia (HPP) is a rare heritable metabolic bone disease caused by hypomorphic mutations in the ALPL (in human) or Akp2 mouse) gene, encoding tissue-nonspecific alkaline phosphatase (TNAP) enzyme. In addition to skeletal and dental malformations, severe forms of HPP are also characterized presence spontaneous seizures. Initially, these seizures were attributed an impairment GABAergic neurotransmission altered vitamin B6 metabolism. However, recent work our group using knockout mice...
The ionotropic ATP-gated P2X7 receptor is an important contributor to inflammatory signaling cascades via the release of Interleukin-1β, as well having roles in cell death, neuronal plasticity and neurotransmitters. Accordingly, there interest targeting for treatment epilepsy. However, pathways downstream activation remain incompletely understood. Notably, recent studies showed that expression controlled, part, by microRNAs (miRNAs). Here, we explored receptor-dependent microRNA comparing...
Abstract Activation of the ATP-gated P2X7 receptor (P2X7R), implicated in numerous diseases brain, can trigger diverse responses such as release pro-inflammatory cytokines, modulation neurotransmission, cell proliferation or death. However, despite known species-specific differences its pharmacological properties, to date, most functional studies on P2X7R have been analyzed cells from rodents immortalised lines. To assess endogenous and expression P2X7Rs human astrocytes, we differentiated...
Abstract Objective Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large‐scale changes hippocampus mice during epilepsy development. The cytoplasmic element‐binding CPEB4 was found drive epilepsy‐induced poly(A) tail changes, lacking...
<title>Abstract</title> The P2X7 receptor (P2X7R) is a cation-permeable ionotropic activated by extracellular adenosine 5’-triphosphate (ATP) which has been implicated in numerous diseases of the CNS, including epilepsy. Activation P2X7R can trigger diverse responses release pro-inflammatory cytokines, modulation neurotransmission, cell proliferation or death. There have conflicting reports on cellular identity P2X7R-expressing cells brain. Expression P2X7Rs well documented microglia and...
Abstract Objective Pharmacoresistance and the lack of disease-modifying actions current anti-seizure drugs persist as major challenges in treatment epilepsy. Experimental models chemoconvulsant-induced status epilepticus remain choice to discover potential anti-epileptogenic but doubts extent which they model human pathophysiology. The aim present study was compare molecular landscape intraamygdala kainic acid mice with findings resected brain tissue from patients drug-resistant temporal...
Background and Purpose Refractory status epilepticus is a clinical emergency associated with high mortality morbidity. Increasing evidence suggests neuroinflammatory pathways contribute to the development of drug-refractoriness during epilepticus. The ATP-gated P2X7 receptor (P2X7R) has been described as potential link between inflammation increased hyperexcitability. aim present study was determine contribution P2X7R drug-refractory its therapeutic potential. Experimental Approach Status...