A5030083663- Receptor Mechanisms and Signaling
- Adenosine and Purinergic Signaling
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Neuropeptides and Animal Physiology
- Lipid Membrane Structure and Behavior
- Chromatography in Natural Products
- Neurotransmitter Receptor Influence on Behavior
- Protein Kinase Regulation and GTPase Signaling
- Hippo pathway signaling and YAP/TAZ
- Neurological disorders and treatments
- Flavonoids in Medical Research
- Cholesterol and Lipid Metabolism
- HER2/EGFR in Cancer Research
- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Biochemical effects in animals
- Peroxisome Proliferator-Activated Receptors
- Anesthesia and Neurotoxicity Research
- Chemical Synthesis and Analysis
- Fatty Acid Research and Health
- Nerve injury and regeneration
- Pharmacological Effects and Assays
Discovery Institute
2019-2024
Sanford Burnham Prebys Medical Discovery Institute
2019-2024
Universitat de Barcelona
2011-2021
Institut d'Investigació Biomédica de Bellvitge
2010-2021
Abstract Membrane levels of docosahexaenoic acid (DHA), an essential omega-3 polyunsaturated fatty (ω-3 PUFA), are decreased in common neuropsychiatric disorders. DHA modulates key cell membrane properties like fluidity, thereby affecting the behaviour transmembrane proteins G protein-coupled receptors (GPCRs). These receptors, which have special relevance for major disorders recently been shown to form dimers or higher order oligomers and evidence suggests that affect GPCR function by...
In the CNS, an antagonistic interaction has been shown between adenosine A(2A) and dopamine D(2) receptors (A(2A)Rs D(2)Rs) that may be relevant both in normal pathological conditions (i.e., Parkinson's disease). Thus, molecular determinants mediating this receptor-receptor have recently explored, as fine tuning of target (namely A(2A)R/D(2)R oligomer) could possibly improve treatment certain CNS diseases. Here, we used a fluorescence resonance energy transfer-based approach to examine...
Abstract Parkinson’s disease (PD) is a dopaminergic-related pathology in which basal ganglia functioning are altered. It has been postulated that direct receptor-receptor – i.e. dopamine D2 receptor (D2R) and adenosine A2A (A2AR) interaction may be finely regulating this brain area. Accordingly, elucidating whether the prompts changes on these structures could grant valuable information for design of new PD therapies. Here, we first resolved long-standing question concerning D2R-A2AR...
The EPH receptor A2 (EphA2) tyrosine kinase plays an important role in a plethora of biological and disease processes, ranging from angiogenesis cancer to inflammation parasitic infections. EphA2 is therefore considered drug target. Two short peptides previously identified by phage display, named YSA SWL, are widely used as EphA2-targeting agents owing their high specificity for this receptor. However, these have only modest (micromolar) potency. Lack structural information on the binding...
The EphA2 receptor tyrosine kinase activates signaling pathways with different, and sometimes opposite, effects in cancer other pathologies. Thus, highly specific potent biased ligands that differentially control responses could be therapeutically valuable. Here, we use EphA2-specific monomeric peptides to engineer dimeric three different geometric configurations combine a potential ability modulate the high potency prolonged residence time characteristic of ligands. readily induce...
Background: Several biophysical techniques have been successfully implemented to detect G protein-coupled receptors (GPCRs) heteromerization. Although these approaches made it possible ascertain the presence of GPCR heteromers in animal models disease, no success has accomplished pathological human post-mortem brains. The AlphaScreen technology consistently used quantify small analyte accumulation or depletion, bimolecular interactions, and post-translational modifications. high...
Caffeine, the most consumed psychoactive substance worldwide, may have beneficial effects on Parkinson's disease (PD) therapy. The mechanism by which caffeine contributes to its antiparkinsonian acting as either an adenosine A2A receptor (A2AR) neutral antagonist or inverse agonist is unresolved. Here we show that A2AR in cell-based functional studies and experimental parkinsonism. Thus, observed triggers a distinct mode, opposite agonist, of receptor's activation switch leading suppression...
Parkinson's disease (PD) is a neurodegenerative disorder of unknown etiology. The main treatment PD consists medication with dopamine-based drugs, which palliate the symptoms but may produce adverse effects after chronic administration. Accordingly, there need to develop novel neuroprotective therapies. Several studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFA) might provide protection against brain damage. Here, we studied several experimental models PD, using striatal...
Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca 2+ wave-dependent activation of small-conductance -activated K + (SK) channels. Here, we show that mGlu 5 and SK2 channels coassemble in heterologous coexpression systems rat brain. Further, cotransfected cells or primary neurons, receptor stimulation activated apamin-sensitive SK2-mediated currents. In addition, promoted plasma membrane targeting both proteins correlated with...
We have developed a novel methodology for monitoring the σ1 receptor activation switch in living cells. Our assay uncovered intrinsic nature of ligands by recording ligand-mediated conformational changes this chaperone protein. The change triggered each ligand correlated well with its ability to attenuate formalin induced nociception an animal model pain. This tool may assist predicting antinociceptive efficacy ligands.
The Eph receptor tyrosine kinases and their ephrin ligands regulate many physiological pathological processes. EphA4 plays important roles in nervous system development adult homeostasis, while aberrant signaling has been implicated neurodegeneration. may also affect cancer malignancy, but the regulation effects of are poorly understood. A correlation between decreased patient survival high mRNA expression melanoma tumors that highly express ephrinA suggests enhanced contribute to...
Worldwide, stroke is the main cause of long-term adult disability. After initial insult, most patients undergo a subacute period with intense plasticity and rapid functional improvements. This followed by chronic phase where recovery reaches plateau that only partially modifiable rehabilitation. experimental stroke, various rehabilitation paradigms improve recovery. However, in order to reach best possible outcome, combination plasticity-promoting strategies might be necessary. EphA4...
Missense mutations in the EPHA1 receptor tyrosine kinase have been identified Alzheimer's patients. To gain insight into their potential role disease pathogenesis, we investigated effects of four these mutations. We show that P460L mutation second fibronectin type III (FN2) domain drastically reduces cell surface localization while increasing phosphorylation surface-localized receptor. The R791H abolishes phosphorylation, indicating abrogation kinase-dependent signaling. Furthermore, both...
The existence of a supramolecular organization the G protein-coupled receptor (GPCR) is now being widely accepted by scientific community. Indeed, GPCR oligomers may enhance diversity and performance which extracellular signals are transferred to proteins in process transduction, although mechanism that underlies this phenomenon still remains unsolved. Recently, it has been proposed trans-conformational switching model could be allowing direct inhibition/activation activation/inhibition,...