A5020836602- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- Inflammation biomarkers and pathways
- Tryptophan and brain disorders
- Immune Response and Inflammation
- Nerve injury and regeneration
- Immune cells in cancer
- Neonatal and fetal brain pathology
- Spinal Cord Injury Research
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Nitric Oxide and Endothelin Effects
- Traumatic Brain Injury and Neurovascular Disturbances
- S100 Proteins and Annexins
- Neurogenesis and neuroplasticity mechanisms
- Bacteriophages and microbial interactions
- Cell Adhesion Molecules Research
- Viral Infectious Diseases and Gene Expression in Insects
- Mitochondrial Function and Pathology
- Anesthesia and Neurotoxicity Research
- Phagocytosis and Immune Regulation
- Adenosine and Purinergic Signaling
Institut Pasteur de Montevideo
2012-2023
Universitat de Barcelona
2022-2023
Universidad de Montevideo
2001-2023
Universidad de la República
2004-2022
Royal Holloway University of London
2012
Institut Pasteur
2011
Universitat Autònoma de Barcelona
2002-2009
Instituto de Investigaciones Biológicas Clemente Estable
1997-2001
During pathology of the nervous system, increased extracellular ATP acts both as a cytotoxic factor and pro-inflammatory mediator through P2X(7) receptors. In animal models amyotrophic lateral sclerosis (ALS), astrocytes expressing superoxide dismutase 1 (SOD1G93A) mutations display neuroinflammatory phenotype contribute to disease progression motor neuron death. Here we studied role acting receptors an initiator neurotoxic that leads astrocyte-mediated death in non-transgenic SOD1G93A...
Abstract Oxidative stress mediated by nitric oxide (NO) and its toxic metabolite peroxynitrite has previously been associated with motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Degenerating spinal neurons familial sporadic ALS are typically surrounded reactive astrocytes expressing the inducible form of NO synthase (iNOS), suggesting that astroglia may have a pathogenic role ALS. We report here brief exposure cord astrocyte monolayers to (0.25–1 mM) provoked long‐lasting...
It has recently become evident that activating/inhibitory cell surface immune receptors play a critical role in regulating and inflammatory processes the central nervous system (CNS). The immunoreceptor CD300f expressed on monocytes, neutrophils, mast cells modulates inflammation, phagocytosis, outcome models of autoimmune demyelination, allergy, systemic lupus erythematosus. On other hand, finely regulated response is essential to induce regeneration after injury peripheral nerves since...
Inflammation is an important determinant of the severity and outcome central nervous system injury. The endogenous anti-inflammatory cytokine interleukin-10 (IL-10) upregulated in injured adult where it controls terminates inflammatory processes. developing brain, however, displays differences susceptibility to insults associated responses from brain; anatomic temporal patterns injury-induced IL-10 expression immature brain after excitotoxic injury are unknown. We analyzed spaciotemporal...
A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors become a central topic many neurological conditions. We explored preclinical and clinical evidence the CD300f receptor fine regulation its contribution to MDD. found that prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) human cytoplasmic tail inhibits protein kinase C phosphorylation threonine is...
Abstract Peroxynitrite‐dependent tyrosine nitration has been postulated to be involved in motor neuron degeneration amyotrophic lateral sclerosis (ALS). Evidence supporting this supposition includes the appearance of both free and protein‐linked 3‐nitro‐ l ‐tyrosine (nitrotyrosine) sporadic familial ALS, as well increased nitrotyrosine levels spinal cord transgenic mice expressing ALS‐linked superoxide dismutase mutants at symptom onset. Here we demonstrate that incubation with clinically...
Abstract It is well established that after adult brain damage the enzymes cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) play an important role in inflammatory processes oxidative stress, which are considered to be leading factors contributing delayed cell death. The contribution of these postnatal damage, however, poorly understood. In our study, excitotoxic lesions were induced by injection N ‐methyl‐ D ‐aspartate cortex day 9 rats. After different survival times...
Abstract Background In the nervous system, as in other organs, Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key antioxidant enzyme involved detoxification normal cellular metabolism and after cell injury. Although it has been suggested that immature brain different susceptibility to oxidative damage than adult brain, distribution cell-specific expression of this postnatal not documented. Methods study, we used immunohistochemistry western blot analyze SOD intact rat an NMDA-induced...
Abstract It is well known that cell surface immune receptors play a critical role in regulating and inflammatory processes the central nervous system (CNS). We have analyzed function of cluster differentiation (CD)300f immunoreceptor model excitotoxic rat brain damage. First, to explore presence endogenous ligand(s) for this receptor we used human CD300f‐Ig soluble protein confocal microscopy, showing specific staining mainly CNS white matter on oligodendrocytes certain astrocytes. Next,...
Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of transient overexpression antioxidant enzyme Cu/Zn dismutase (SOD) after excitotoxic injury to immature rat brain by using recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with NLSCt carrying SOD or control GFP transgenes 2 hours intracortical...
Oxygen free radicals and nitric oxide (NO) participate in the pathogenesis of acute central nervous system (CNS) injury by forming peroxynitrite, which promotes oxidative damage tyrosine nitration. Neuronal nitration is associated with cell death, but little known characteristics fate nitrated astrocytes. In this study, we have used a postnatal excitotoxic lesion model (intracortical NMDA injection) our aims were (i) to evaluate temporal spatial pattern astroglial correlation...
Aim & Methods: We have produced two chimerical peptides of 10.2 kDa, each contain four biologically active domains, which act as building blocks protein-based nonviral vehicles for gene therapy. In solution, these tend to aggregate amorphous clusters more than 1000 nm, while the presence DNA promotes their architectonic reorganization mechanically stable nanometric spherical entities approximately 80 nm that penetrate mammalian cells through arginine–glycine–aspartic acid cell-binding...
CMRF35-like molecule-1 (CLM-1) belongs to a receptor family mainly expressed in myeloid cells that include activating and inhibitory receptors. CLM-1 contains two ITIMs single immunoreceptor tyrosine-based switch motif (ITSM), although also displays binding site for p85α regulatory subunit of PI3K. By using murine primary microglial cultures, we show the presence all CLM members characterize expression both basal conditions during activation. The TLR4 agonist lipopolysaccharide (LPS) TLR3...
Successful introduction of therapeutic genes into the central nervous system (CNS) requires further development efficient transfer vehicles that avoid viral vector-dependent adverse reactions while maintaining high transfection efficiency. The multifunctional protein 249AL was recently constructed for in vitro gene delivery. Here, we explore capability this vector vivo delivery to postnatal rat CNS. Significant transgene expression observed both excitotoxically injured and noninjured brain...
Abstract Objective Integrin binding to extracellular matrix ligands, including those presenting RGD motifs, modulate diverse cellular processes. In the brain, many endogenous RGD‐containing molecules are induced after damage. Previously, gene therapy vector termed NLSCt, which displays an motif, was shown neuroprotect immature brain excitotoxicity. We analyze whether neuroprotection is mediated by motif. Methods synthetic peptide GPenGRGDSPCA (GPen) injected 2 hours N ‐methyl‐ D...
Herein, we have used bioinformatics tools to predict five clusters defining ligand-binding sites on the extracellular domain of human CD300b receptor, presumably involved in formation both homodimers and heterodimers with other CD300 family members. Site-directed mutagenesis revealed residues glutamic acid 28 glutamine 29 cluster 5 be necessary for complexes. Surprisingly, disruption 2 4 reconstituted binding capability lost by mutation alanine, alanine (E28A-Q29G). We identified a missense...