A5052065176- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Infectious Encephalopathies and Encephalitis
- Porphyrin Metabolism and Disorders
- Neonatal Health and Biochemistry
- Amino Acid Enzymes and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Alcoholism and Thiamine Deficiency
- Photochromic and Fluorescence Chemistry
- Microbial metabolism and enzyme function
- DNA and Nucleic Acid Chemistry
- Endoplasmic Reticulum Stress and Disease
- Advanced NMR Techniques and Applications
- Supramolecular Self-Assembly in Materials
- Viral Infections and Immunology Research
- Supramolecular Chemistry and Complexes
- Animal Ecology and Behavior Studies
- Bladder and Urothelial Cancer Treatments
- Metabolism and Genetic Disorders
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
CIC bioGUNE
2016-2025
Centro de Investigación Biomédica en Red
2022-2025
Instituto de Salud Carlos III
2022-2025
Ikerbasque
2024
Euskadiko Parke Teknologikoa
2012-2022
Universitat Autònoma de Barcelona
2015
Significance This contribution reports on the application of gold nanorods to detection amyloids in Parkinson’s and prion diseases. We found that show no interaction with monomeric proteins but adsorb onto helical protein fibrils. Chiral amyloid templates induce arrangement nanorods, giving rise intense optical activity at plasmon resonance wavelengths. report shows use fibrils as for chiral nanoparticle assembly development a biodetection technique. this effect model recombinant protein,...
Abstract Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding endogenous prion protein (PrP C ) into pathogenic form Sc ). This process, despite being central event underlying these disorders, remains largely unknown at molecular level, precluding prediction new potential outbreaks or interspecies transmission incidents. In this work, we present method to generate bona fide recombinant prions de novo, allowing comprehensive analysis across...
The off-patent marketed antifungal ciclopirox improves symptoms in a mouse model of congenital erythropoietic porphyria.
Prion diseases, particularly sporadic cases, pose a challenge due to their complex nature and heterogeneity. The underlying mechanism of the spontaneous conversion from PrP C Sc , hallmark prion remains elusive. To shed light on this process involvement cofactors, we have developed an in vitro system that faithfully mimics misfolding using minimal components. By employing PMSA methodology introducing isoleucine residue at position 108 mouse PrP, successfully generated recombinant murine...
Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as Creutzfeldt-Jakob disease are the vast majority. Unlike genetic acquired of disease, these idiopathic occur seemingly due to a random event spontaneous misfolding cellular PrP (PrPC) into pathogenic isoform (PrPSc). Currently, molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling...
One of the characteristics prions is their ability to infect some species but not others and prion resistant have been special interest because potential in deciphering determinants for susceptibility. Previously, we developed different vitro vivo models assess susceptibility that were erroneously considered infection, such as members Leporidae Equidae families. Here undertake approaches understand unresolved low canids. Studies based on amino acid sequence canine protein (PrP), together...
Unlike other species, prion disease has never been described in dogs even though they were similarly exposed to the bovine spongiform encephalopathy (BSE) agent. This resistance prompted a thorough analysis of canine PRNP gene and presence negatively charged amino acid residue position 163 was readily identified as potentially fundamental it differed from all known susceptible species. In present study, first transgenic mouse model expressing dog protein (PrP) generated challenged...
Each known abnormal prion protein (PrPSc) is considered to have a specific range and therefore the ability infect some species not others. Consequently, been assumed be disease resistant as no successful natural or experimental challenge infections reported. This assumption suggested that, independent of virulence PrPSc strain, normal (PrPC) from these 'resistant' could induced misfold. Numerous in vitro vivo studies trying corroborate unique properties undertaken. The results presented...
Abstract Misfolded prion protein aggregates (PrP Sc ) show remarkable structural diversity and are associated with highly variable disease phenotypes. Similarly, other proteins, including amyloid-β, tau, α-synuclein, serum amyloid A, misfold into distinct conformers linked to different clinical diseases through poorly understood mechanisms. Here we use mice expressing glycophosphatidylinositol (GPI)-anchorless protein, PrP C , together hydrogen-deuterium exchange coupled mass spectrometry...
The resolution of the three-dimensional structure infectious prions at atomic level is pivotal to understand pathobiology Transmissible Spongiform Encephalopathies (TSE), but has been long hindered due certain particularities these proteinaceous pathogens. Difficulties related their purification from brain homogenates disease-affected animals were resolved almost a decade ago by development in vitro recombinant prion propagation systems giving rise highly prions. However, lack knowledge...
Interspecies transmission of prions is a well-established phenomenon, both experimentally and under field conditions. Upon passage through new hosts, prion strains have proven their capacity to change properties this source strain diversity which needs be considered when assessing the potential risks associated with consumption contaminated protein sources. Rabbits were for decades resistant species until otherwise recently. To determine extent rabbit susceptibility assess effects different...
Prions are deadly infectious agents made of PrPSc, a misfolded variant the cellular prion protein (PrPC) which self-propagates by inducing misfolding native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), be resistant to potential drugs, or acquire drug resistance, hampering development effective therapies. We identified Zn(II)-BnPyP, tetracationic porphyrin that binds distinct domains PrPC, eliciting dual anti-prion effect. Zn(II)-BnPyP binding C-terminal pocket...
Abstract The first case of CWD in a Norwegian red deer was detected by routine ELISA test and confirmed western blotting immunohistochemistry the brain stem animal. Two different tests were conducted independently two laboratories, showing that glycoprofile from reindeer moose North American CWD. isolate showed nevertheless features similar to classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on PrP Sc staining brainstem absence detectable lymphoid tissues. Because...
Prion diseases are a group of neurodegenerative disorders that can be spontaneous, familial or acquired by infection. The conversion the prion protein PrPC to its abnormal and misfolded isoform PrPSc is main event in pathogenesis all origins. In spontaneous diseases, mechanisms trigger formation central nervous system remain unknown. Several reports have demonstrated accumulation induce endoplasmic reticulum (ER) stress proteasome impairment from early stages disease. Both lead an increment...
ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of rare progressive neurodegenerative disorders caused by an abnormally folded prion protein (PrP Sc ). This is capable transforming the normal cellular C ) into new infectious PrP . Interspecies transmissibility studies performed experimental challenge and outbreak bovine encephalopathy that occurred in late 1980s 1990s showed while some species (sheep, mice, cats) readily susceptible to TSEs, others...
Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and individual subunits stack to form amyloid fibers. We recently used limited proteolysis map β-strands connecting loops make up solenoid. Using high resolution SDS-PAGE followed by epitope analysis, mass spectrometry, we identified positions ~116/118, 133–134, 141, 152–153, 162, 169 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such likely define and/or borders β-strands, helping...
The description of prions as causal agents Transmissible Spongiform Encephalopathies (TSE), is nowadays accepted an important breakthrough in biology revealed the existence a completely new group pathogens and way transmission for biological information. A common feature many neurodegenerative disorders presence protein aggregates nervous system evidences highlighting similarities these proteins with TSE-causing increase, line separating infectious from other becomes thinner than previously...
Human transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders that include Kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome (GSS), and familial insomnia. GSS is genetically determined TSE caused by range mutations within the protein (PrP) gene. Several animal models, based on expression PrPs carrying analogous to human heritable diseases, support might predispose PrP spontaneously misfold. An adapted Protein...