A5064569500- Lysosomal Storage Disorders Research
- Trypanosoma species research and implications
- Cellular transport and secretion
- Hearing, Cochlea, Tinnitus, Genetics
- Glycogen Storage Diseases and Myoclonus
- Muscle Physiology and Disorders
- Carbohydrate Chemistry and Synthesis
- Nuclear Structure and Function
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- S100 Proteins and Annexins
- Ion Channels and Receptors
- Protease and Inhibitor Mechanisms
- Protein Tyrosine Phosphatases
- Frailty in Older Adults
- Growth Hormone and Insulin-like Growth Factors
- Chronic Lymphocytic Leukemia Research
- Connexins and lens biology
- T-cell and B-cell Immunology
- Genetics and Neurodevelopmental Disorders
- Vestibular and auditory disorders
- Biomedical Research and Pathophysiology
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Virus-based gene therapy research
Galicia Sur Biomedical Foundation
2018-2024
Servicio Gallego de Salud
2014-2024
Universidade de Vigo
2016-2024
Instituto de Investigación Sanitaria de Santiago
2016
University Hospital Complex Of Vigo
2010-2015
Complexo Hospitalario Universitario A Coruña
2012
Veneto Institute of Molecular Medicine
2007-2010
University of Padua
2007-2008
National Institute of Allergy and Infectious Diseases
2006
National Institutes of Health
2006
Extracellular ATP controls various signaling systems including propagation of intercellular Ca 2+ signals (ICS). Connexin hemichannels, P2x7 receptors (P2x7Rs), pannexin channels, anion vesicles, and transporters are putative conduits for release, but their involvement in ICS remains controversial. We investigated cochlear organotypic cultures, which acts as an IP 3 -generating agonist evokes responses that have been linked to noise-induced hearing loss development hair cell-afferent...
In this study, we demonstrate that the in vitro interactions between a CD56(neg)/CD16(pos) (CD56(neg)) subset of natural killer (NK) cells and autologous dendritic (DCs) from HIV-1-infected viremic but not aviremic individuals are markedly impaired likely interfere with development an effective immune response. Among defective abnormalities process reciprocal NK-DC activation maturation as well defect NK cell-mediated editing or elimination immature DCs (iDCs). Notably, lysis mature (mDCs)...
Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis Alzheimer's disease (AD). Particularly, mitochondrial dysfunction is a hallmark amyloid-beta-induced neuronal toxicity disease. The recent emphasis on intracellular biology amyloid-beta its precursor protein (APP) has led researchers to consider possibility that mitochondria-associated directly cause neurotoxicity. Both proteins are known localize membranes, block transport...
Low density lipoprotein receptor-related protein (LRP) belongs to the low-density receptor family, generally recognized as cell surface endocytic receptors, which bind and internalize extracellular ligands for degradation in lysosomes. Neurons require cholesterol function keep membrane rafts stable. Cholesterol uptake into neuron is carried out by ApoE via LRPs receptors on surface. In neurons most important are LRP-1 LRP-2, even it thought that a causal factor Alzheimer's disease (AD)...
Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of course are complicated clinical heterogeneity FD, as well frequently inconclusive biochemical genetic test results that do not correlate with course. We sought to identify potential biomarkers FD better understand underlying pathophysiology phenotypes. compared plasma proteomes 50 patients matched healthy controls using DDA SWATH-MS....
Ca2+ enters the stereocilia of hair cells through mechanoelectrical transduction channels opened by deflection bundle and is exported back to endolymph an unusual splicing isoform (w/a) plasma-membrane calcium-pump 2 (PMCA2). Ablation or missense mutations pump cause deafness, as described for G283S mutation in deafwaddler (dfw) mouse. A deafness-inducing PMCA2 (G293S) has been identified a human family. The family also was screened cadherin 23, which accentuated hearing loss previously with...
Connexin 26 (Cx26) and connexin 30 (Cx30) are encoded by two genes ( GJB2 GJB6 , respectively) that found within 50 kb in the same complex deafness locus, DFNB1. Immunocytochemistry quantitative PCR analysis of Cx30 KO mouse cultures revealed Cx26 is downregulated at protein level mRNA nonsensory cells located between outer hair stria vascularis. To explore coregulation, we manipulated gene expression using bovine adeno-associated virus. Overexpression transduction with virus restored...
In 2001, we reported linkage of an autosomal dominant form limb-girdle muscular dystrophy, dystrophy 1F, to chromosome 7q32.1-32.2, but the identity mutant gene was elusive. Here, using a whole genome sequencing strategy, identified causative mutation heterozygous single nucleotide deletion (c.2771del) in termination codon transportin 3 (TNPO3). This is situated within chromosomal region linked disease and encodes nuclear membrane protein belonging importin beta family. TNPO3 transports...
Lafora disease is an autosomal recessive form of progressive myoclonic epilepsy caused by defects in the EPM2A and EPM2B genes. Primary symptoms pathology include seizures, ataxia, myoclonus, development severe dementia. can be gene, which encodes laforin protein phosphatase, or NHLRC1 gene (also called EPM2B) codifying malin E3 ubiquitin ligase. Studies on cellular models showed that interact operate as a functional complex apparently regulating functions such glycogen metabolism, stress...
Fabry disease is an X-linked lysosomal storage disorder caused by the impairment of α-galactosidase A. Enzyme replacement therapy available to treat patients, who often experience delayed diagnosis. A newborn screening for was performed study prevalence pathology and evaluate possibility implement test in systematic screenings. We collected 14,600 dried blood spot samples (7575 males 7025 females) carried out a diagnostic fluorometric measurement enzymatic activity GLA gene sequencing....
Progressive hearing loss is common in the human population, but we have few clues to molecular basis. Mouse mutants with progressive offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis a useful way of generating models. We characterised new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance impairment. Obl/+ showed increasing impairment from post-natal day (P)20 P90, auditory function was followed by corresponding base apex progression...
The mechanotransduction process in hair cells the inner ear is associated with influx of calcium from endolymph. Calcium exported back to endolymph via splice variant w/a PMCA2 stereocilia membrane. To further investigate role pump, we have identified and characterized a novel ENU-induced mouse mutation, Tommy, gene. mutation causes non-conservative E629K change second intracellular loop pump that harbors active site. Tommy mice show profound hearing impairment P18, significant differences...
Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events endothelial dysfunction. In spite efficacy demonstrated by enzyme replacement therapy pharmacological chaperones in delaying progression, few studies have analyzed whether these treatments can improve...
B lymphocyte chemokine receptors signal to downstream effectors by activating heterotrimeric G proteins. However, many of these remain unknown and the known ones often have ill-defined roles in cell trafficking. Here we report that pharmacological inhibitors phosphoinositide 3-kinases (wortmannin, WMN), Bruton's tyrosine kinase (LFM-A13), Jun kinases (SP600125) all significantly impair CXCL12-induced mouse chemotaxis a human lymphoma line. Examination two CXCR4-induced signaling pathways...
Fabry disease is a multisystemic lysosomal storage disorder caused by the impairment of α-galactosidase A. The incidence this rare underestimated due to delayed diagnosis. Moreover, management identified subjects often complicated detection variants unclear diagnostic interpretation, usually in screening studies. We performed an observational study based on biochemical and genetic analysis 805 dried blood spot samples from patients with clinical symptoms or family history pathology, which...