A5081698769- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Neurological diseases and metabolism
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Cannabis and Cannabinoid Research
- Virus-based gene therapy research
- RNA modifications and cancer
- Neurogenetic and Muscular Disorders Research
- Metabolism and Genetic Disorders
- Lipid metabolism and biosynthesis
- RNA Interference and Gene Delivery
- Biochemical Acid Research Studies
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Alcoholism and Thiamine Deficiency
- Endoplasmic Reticulum Stress and Disease
Duran i Reynals Hospital
2023-2024
Institut d'Investigació Biomédica de Bellvitge
2010-2024
Centre for Biomedical Network Research on Rare Diseases
2010-2024
Instituto de Salud Carlos III
2011-2024
Centro de Investigación Biomédica en Red
2011-2023
Biomedical Research Institute
2022
Universitat de Barcelona
2015
Bellvitge University Hospital
2013
X-linked adrenoleukodystrophy (X-ALD) is a fatal, axonal demyelinating, neurometabolic disease. It results from the functional loss of member peroxisomal ATP-binding cassette transporter subfamily D (ABCD1), which involved in metabolism very long-chain fatty acids (VLCFA). Oxidative damage proteins caused by excess hexacosanoic acid, most prevalent VLCFA accumulating X-ALD, an early event neurodegenerative cascade. We demonstrate here that valproic acid (VPA), widely used anti-epileptic drug...
Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number neurodegenerative conditions. To investigate intertwining both noxious factors, we have chosen mouse model adrenoleukodystrophy (X-ALD), which exhibits degeneration spinal cords motor disability. The disease is caused by loss function ABCD1 transporter, involved import degradation very long-chain fatty acids (VLCFA) peroxisomes. Oxidative due to VLCFA excess...
X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic disease characterized by the accumulation of very long chain fatty acids (VLCFAs) due to loss function peroxisomal transporter ABCD1. Here, using in vivo and vitro models, we demonstrate that autophagic flux was impaired elevated mammalian target rapamycin (mTOR) signaling, which contributed X-ALD pathogenesis. We also show excess VLCFAs downregulated autophagy human fibroblasts. Furthermore, mTOR inhibition derivative...
<h3>Background and Objectives</h3> Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half all patients. We aimed determine the clinical utility singleton whole-exome sequencing whole-genome (sWES-WGS) interpreted phenotype- interactome-driven prioritization algorithm diagnose GWMD while identifying novel phenotypes candidate genes. <h3>Methods</h3> A case series...
Oxidative damage is a pivotal aetiopathogenic factor in X-linked adrenoleukodystrophy. This neurometabolic disease characterized by the accumulation of very-long-chain fatty acids owing to loss function peroxisomal transporter Abcd1. Here, we used adrenoleukodystrophy mouse model and patient's fibroblasts detect malfunctioning ubiquitin–proteasome system resulting from oxidatively modified proteins, some involved bioenergetic metabolism. Furthermore, immunoproteasome machinery appears...
X-linked adrenomyeloneuropathy (AMN) is an inherited neurometabolic disorder caused by malfunction of the ABCD1 gene, characterized slowly progressing spastic paraplegia affecting corticospinal tracts, and adrenal insufficiency. AMN most common phenotypic manifestation adrenoleukodystrophy (X-ALD). In some cases, inflammatory cerebral demyelination occurs associated to poor prognosis in (cAMN). Though codes for a peroxisomal transporter very long-chain fatty acids, molecular mechanisms that...
The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic loss-of-function who presented early onset spastic paraplegia, ataxia, optic nerve hypoplasia, dysmorphic features, broadening previously described phenotype. Our functional lipidomic analyses provided evidence that...
Abstract Pelizaeus‐Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD caused variations in the proteolipid protein gene PLP1 , which encodes two major myelin proteins central nervous system, PLP its spliced isoform DM20, oligodendrocytes. Large duplications including entire are most frequent causative mutation leading to classical form PMD. The Plp1...
Abstract Background Whole-exome sequencing (WES) and whole-genome (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms maximise WES/WGS diagnostic yield in disease patients. Most devoted this aim take advantage of patient phenotype information prioritization genomic data, although are often limited by incomplete gene-phenotype knowledge stored biomedical databases a lack proper...