A5087735763- Endoplasmic Reticulum Stress and Disease
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Infant Nutrition and Health
- Birth, Development, and Health
- Neurogenetic and Muscular Disorders Research
- Iron Metabolism and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Heat shock proteins research
- Metabolism and Genetic Disorders
- Porphyrin Metabolism and Disorders
- Advanced Electron Microscopy Techniques and Applications
- Cell Image Analysis Techniques
- Immunotoxicology and immune responses
- Child Nutrition and Feeding Issues
- Viral Infections and Vectors
- interferon and immune responses
- CRISPR and Genetic Engineering
- Transgenic Plants and Applications
- Breastfeeding Practices and Influences
- Mosquito-borne diseases and control
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
Universidad de Navarra
2011-2024
Navarre Institute of Health Research
2020-2024
Instituto de Salud Pública de Navarra
2018
University of Turin
1984-1986
Ospedale Regina Margherita
1986
Abstract Loss of protein folding homeostasis features many the most prevalent neurodegenerative disorders. As coping mechanism to stress within endoplasmic reticulum (ER), unfolded response (UPR) comprises a set signaling mechanisms that initiate gene expression program restore proteostasis, or when is chronic overwhelming promote neuronal death. This fate-defining capacity UPR has been proposed play key role in amyotrophic lateral sclerosis (ALS). However, several genetic pharmacological...
Acute intermittent porphyria (AIP) results from haplo-insufficient activity of porphobilinogen deaminase (PBGD) and is characterized clinically by life-threatening, acute neurovisceral attacks. To date, liver transplantation the only curative option for AIP. The aim present preclinical nonhuman primate study was to determine safety transduction efficacy an adeno-associated viral vector encoding PBGD (recombinant AAV serotype 5-codon-optimized human deaminase, rAAV5-cohPBGD) administered...
The integrated stress response (ISR) regulates translation in to diverse stresses. ISR activation has been documented amyotrophic lateral sclerosis (ALS) patients and ALS experimental models. In models, both stimulation inhibition prevented neurodegeneration; however, which mode of regulation would work is still debated. We previously demonstrated that the modulator ISRIB (Integrated Stress Response InhiBitor, an eIF2B activator) enhances survival neurons expressing neurotoxic allele SOD1...
Endoplasmic reticulum (ER) to nucleus homeostatic signaling, known as the unfolded protein response (UPR), relies on non-canonical splicing of XBP1 mRNA. The molecular switch that initiates is oligomerization ER stress sensor and UPR endonuclease IRE1α (inositol-requiring enzyme 1 alpha). While can form large clusters have been proposed function processing centers ER, actual oligomeric state active complexes well targeting mechanism recruits oligomers remains unknown. Here, we developed a...
Early life events are associated with the susceptibility to chronic diseases in adult life. Perturbations of endoplasmic reticulum (ER) homeostasis activate unfolded protein response (UPR), which contributes development metabolic alterations. Our aim was evaluate liver UPR an animal model intrauterine growth restriction (IUGR). A significantly increased expression X-box binding protein-1 spliced (XBP1s) mRNA (p<0.01), Endoplasmic Reticulum-localized DnaJ homologue (Erdj4) (p<0.05) and...
Abstract The innate immune system provides a primary line of defense against pathogens. Stimulator IFN genes (STING), encoded by the TMEM173 gene, is critical protein involved in IFN-β induction response to infection different In this study, we describe expression three alternative-spliced human (h) mRNAs producing STING truncated isoforms 1, 2, and 3 addition full-length wild-type (wt) hSTING. All lack exon 7 share N-terminal transmembrane region with wt Overexpression failed induce IFN-β,...
<title>Abstract</title> The disruption of protein folding homeostasis in motoneurons (MNs), and the ensuing accumulation aggregates, is one main molecular hallmarks amyotrophic lateral sclerosis (ALS) pathology, has been recapitulated cellular animal disease models. loss proteostasis other stresses MN trigger activation a general stress mechanism, integrated response (ISR). ISR initiated by either four stress-sensing kinases (GCN2, HRI, PERK PKR) which, upon distinct insults, promote...
Abstract Endoplasmic reticulum (ER) to nucleus homeostatic signalling, known as the unfolded protein response (UPR), relies on non-canonical splicing of XBP1 mRNA. The molecular switch that initiates is oligomerization ER stress sensor and UPR endonuclease IRE1α. While IRE1α can form large clusters have been proposed function processing centers ER, actual oligomeric state active complexes well targeting mechanism recruits oligomers, remain unknown. Here, we used a single molecule imaging...
Tight control of transgene expression is key to ensure the efficacy a wide range gene therapy interventions, in which magnitude and duration have be adjusted therapeutic needs, thereby limiting secondary effects. The development upgraded strategies link pathological stress episodes an unmet need therapy. Here, we propose strategy that associates intracellular coping mechanism, unfolded protein response. Specifically, harnessed cis elements required sustain noncanonical splicing X-box binding...