A5009723189- RNA modifications and cancer
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Glioma Diagnosis and Treatment
- Neuroscience and Neural Engineering
- Endoplasmic Reticulum Stress and Disease
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
- Traumatic Brain Injury and Neurovascular Disturbances
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
- Cell Image Analysis Techniques
- Metalloenzymes and iron-sulfur proteins
- Neuroscience and Neuropharmacology Research
- Anesthesia and Neurotoxicity Research
- Genomics, phytochemicals, and oxidative stress
- Genetic Neurodegenerative Diseases
Centro de Investigacion Principe Felipe
2012-2024
Universitat Politècnica de València
2024
Recent evidences highlight the importance of mitochondria-nucleus communication for clinical phenotype oxidative phosphorylation (OXPHOS) diseases. However, participation small non-coding RNAs (sncRNAs) in this has been poorly explored. We asked whether OXPHOS dysfunction alters production a new class sncRNAs, mitochondrial tRNA fragments (mt tRFs), and, if so, mt tRFs play physiological role and their accumulation is controlled by action modification enzymes. To address these questions, we...
The schizophrenia risk gene NRG1 controls the formation of excitatory and inhibitory synapses in cortical circuits. While expression different isoforms occurs during development, adult neurons primarily express CRD-NRG1 isoform characterized by a highly conserved intracellular domain (NRG1-ICD). We others have demonstrated that Nrg1 signaling promotes dendrite elongation connections neuronal development. However, role pathological conditions remains largely unaddressed. Here, we investigated...
Abstract Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel molecular bases underlying disease an infant suffering from ataxia that started at 19 months old and presented severe atrophy peripheral neuropathy early course disease. By whole exome sequencing, we identified novel...
Neuregulin 1 (NRG1) and its receptor ERBB4 are schizophrenia (SZ) risk genes that control the development of both excitatory inhibitory cortical circuits. Most studies focused on characterization ErbB4 deficient mice. However, deletion concurrently perturbs signaling Nrg1 3 (Nrg3), another ligand expressed in cortex. In addition, NRG1 polymorphisms linked to SZ locate mainly non-coding regions they may partially reduce expression. Here, study relevance partial loss-of-function circuits we...
The pathomechanisms underlying oxidative phosphorylation (OXPHOS) diseases are not well-understood, but they involve maladaptive changes in mitochondria-nucleus communication. Many studies on the cross-talk triggered by mitochondrial dysfunction have focused role played regulatory proteins, while participation of miRNAs remains poorly explored. MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is mostly caused mutation m.3243A>G tRNALeu(UUR) gene. Adverse...
Abstract Mitochondrial diseases due to mutations in the mitochondrial (mt) DNA are heterogeneous clinical manifestations but usually include OXPHOS dysfunction. Mechanisms by which dysfunction contributes disease phenotype invoke, apart from cell energy deficit, maladaptive responses mitochondria-to-nucleus retrograde signaling. Here we used five different cybrid models of mtDNA demonstrate that expression nuclear-encoded mt-tRNA modification enzymes TRMU, GTPBP3 and MTO1 varies response...
Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations MTO1 or GTPBP3 impair wobble uridine at position 5 pyrimidine ring and cause heart failure. TRMU affect 2 liver disease. Presently, molecular basis why mutations different genes lead to such clinical symptoms is poorly understood. Here we use Caenorhabditis elegans as a model organism investigate how TRMU, orthologues (designated...
Schizophrenia is associated with altered cortical circuitry. Although the schizophrenia risk gene NRG1 known to affect wiring of inhibitory interneurons, its role in excitatory neurons and axonal development unclear. Here, we investigated Nrg1 corpus callosum, major interhemispheric connection formed by neurons. We found that deletion impaired callosal axon vivo. Experiments vitro vivo demonstrated cell-autonomously required for outgrowth intracellular signaling sufficient promote...
Neuronal loss is at the core of many neuropathologies, including stroke, Alzheimer's disease, and Parkinson's disease. Different methods were developed to study process neuronal survival upon cytotoxic stress. Most are based on biochemical approaches that do not allow single-cell resolution or involve complex costly methodologies. Presented here a versatile, inexpensive, effective experimental paradigm survival. This method takes advantage sparse fluorescent labeling neurons followed by live...
Brain damage is the major cause of permanent disability and it particularly relevant in elderly. While most studies focused on immediate phase neuronal loss upon injury, much less known about process axonal regeneration after damage. The development new refined preclinical models to investigate recovery brain tissue injury a unmet challenge. Here, we present novel experimental paradigm mice that entails (i) tracing cortico-callosal connections, (ii) mechanical lesion motor cortex, (iii)...