A5038202360- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Nanoparticle-Based Drug Delivery
- Inflammasome and immune disorders
- Chemical Synthesis and Analysis
- Nanoplatforms for cancer theranostics
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Click Chemistry and Applications
- Advanced Nanomaterials in Catalysis
- Photosynthetic Processes and Mechanisms
- Genetic Neurodegenerative Diseases
- Venomous Animal Envenomation and Studies
- Lipid Membrane Structure and Behavior
- Signaling Pathways in Disease
- Advanced Breast Cancer Therapies
- Autophagy in Disease and Therapy
- Antimicrobial Peptides and Activities
- Protein Degradation and Inhibitors
- Graphene and Nanomaterials Applications
- Telomeres, Telomerase, and Senescence
Centro de Investigacion Principe Felipe
2016-2025
Universitat Politècnica de València
2014-2024
Universitat de València
2000-2023
Progress (Ireland)
2022
Royal Victoria Eye and Ear Hospital
2022
Centro Médico Sanitas Valencia
2019
Universidade Federal do Ceará
2017
University of Freiburg
2016
Instituto de Biomedicina de Valencia
2008-2014
Hospital General Universitario De Valencia
2008
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease without effective treatment. The progressive motoneuron death in ALS associated with alterations lipid metabolism. As its regulation occurs mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), modulation of mitochondria-ER contacts (MERCs) emerging as crucial factor MAM formation and metabolism control. Using the MERLIN biosensor high-throughput screening within EU-OPENSCREEN ERIC, we discovered small...
Abstract Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis multicellular organisms. Cytochrome c central figure in activation apoptotic intrinsic pathway, thereby activating caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3ε (a direct inhibitor Apaf-1) as cytosolic cytochrome target. Here we explore / show ability block 14-3-3ε-mediated Apaf-1 inhibition, unveiling novel function for an...
Significance Bcl-2 (B-cell lymphoma 2) proteins are key regulators of apoptosis. The recruitment the predominantly cytosolic protein Bax (Bcl-2 associated X, apoptosis regulator) to mitochondria is with mitochondrial outer membrane permeabilization and We report specific interactions between transmembrane domains (TMDs) prosurvival Bcl-x L lymphoma-extra large) proteins. Our results demonstrate that these occur in nonapoptotic human cells participate regulation proteins, introducing concept...
Abstract Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge aging research. We describe the generation fluorogenic probe (sulfonic-Cy7Gal) based on galactose derivative, serve as substrate for β-galactosidase, conjugated Cy7 fluorophore modified sulfonic groups enhance its ability diffuse. When administered male or female mice, β-galactosidase cleaves O-glycosidic bond, releasing that is ultimately...
Myotonic dystrophy type 1 (DM1) is caused by the expansion of noncoding CTG repeats in dystrophia myotonica-protein kinase gene. Mutant transcripts form CUG hairpins that sequester RNA-binding factors into nuclear foci, including Muscleblind-like-1 protein (MBNL1), which regulate alternative splicing and gene expression. To identify molecules target toxic vivo, we performed a positional scanning combinatorial peptide library screen using Drosophila model DM1. The identified D-amino acid...
Abstract The synthesis and characterization of two new capped silica mesoporous nanoparticles for controlled delivery purposes are described. Capped hybrid systems consist MCM‐41 functionalized on the outer surface with polymer ε‐poly‐ L ‐lysine by different anchoring strategies. In both cases, were loaded model dye molecule [Ru(bipy) 3 ] 2+ . An strategy involved random formation urea bonds treatment propyl isocyanate‐functionalized lysine amino groups located backbone (solid Ru‐rLys‐S1 )....
Herein, a novel drug photorelease system based on gold nanostars (AuNSts), coated with mesoporous silica shell and capped paraffin as thermosensitive molecular gate, is reported. Direct measurements of the surface temperature single nanostar irradiated using tightly focused laser beam are performed via heat-sensitive biological matrix. The AuNSt increases by hundreds degrees (°C) even at low powers. AuNSts surfactant-templated synthesis used chemotherapeutic nanocarriers. Synthetic...
Abstract In vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR‐FDA approved Nile blue (NB) dye and capped a galactohexasaccharide ( S3 ). NB emission at 672 nm highly quenched inside , yet remarkable enhancement observed upon cap hydrolysis in presence β‐galactosidase release. The efficacy probe to detect tested vitro melanoma SK‐Mel‐103 breast cancer 4T1 cells palbociclib‐treated BALB/cByJ mice bearing tumor.
Abstract The ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) is an scaffold component of different inflammasomes, intracellular multiprotein platforms the innate immune system that are activated in response to pathogens or damage. formation specks, initiated by inflammasome receptors, promotes and activation procaspase-1, thereby triggering pyroptotic inflammatory cell death pro-inflammatory cytokine release. Here we describe MM01 as...
Changes in the conformation of a peptide anchored onto external surface MCM-41 nanoparticles are used to design temperature-controlled delivery systems.
Abstract New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin B expressing cells are described. Nanometric MCM‐41 supports loaded with safranin O ( S1‐P ) or doxorubicin S2‐P containing a molecular gate based on target peptidic sequence were synthesized. Solids designed to show “zero delivery” and display in the presence of enzyme, which selectively hydrolyzed vitro capping peptide sequence. Controlled delivery HeLa, MEFs WT, lacking cell...
Calcineurin phosphatase plays a crucial role in T cell activation. Dephosphorylation of the nuclear factors activated cells (NFATs) by calcineurin is essential for activating cytokine gene expression and, consequently, immune response. Current immunosuppressive protocols are based mainly on inhibitors, cyclosporine A and FK506. Unfortunately, these drugs associated with severe side effects. Therefore, agents higher selectivity lower toxicity must be identified. The family proteins regulators...
The programmed cell death or apoptosis plays both physiological and pathological roles in biology. Anomalous activation of has been associated with malignancies. intrinsic mitochondrial pathway occurs through a multiprotein complex named the apoptosome. We have discovered molecules that bind to central protein component apoptosome, Apaf-1, inhibits its activity. These new first-in-class apoptosome inhibitors further improved by modifications directed enhance their cellular penetration yield...
Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized a thiolated photolabile molecule (5), whereas the mesoporous face loaded model drug (doxorubicin) capped proton-responsive benzimidazole-β-cyclodextrin supramolecular gatekeepers (N 1). Upon NIR-light, compound 5 photodissociated, resulting in formation of succinic...