Article
Neurosciences
Juliana N. Angelli, Yulli M. Passos, Julyana M. A. Brito, Jerson L. Silva, Yraima Cordeiro, Tuane C. R. G. Vieira
Summary: Prion diseases affect humans and various mammals, with different animals showing varying degrees of resistance to infection. Interaction with biological cofactors can modulate the aggregation of the prion protein, with the N-terminal domain playing a crucial role in efficiency of conversion.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Marie Kostelanska, Karel Holada
Summary: In this study, the efficiency of three phthalocyanine derivatives in photodynamic treatment of seven mouse adapted prion strains originating from different species was investigated. The results showed that the susceptibility of the prion strains to photodynamic oxidative elimination of PrPTSE epitopes varied, and the efficiency of the phthalocyanine derivatives in epitope elimination also differed. This suggests that the structural properties of both the phthalocyanine and the PrPTSE strain may affect the effectiveness of photodynamic prion inactivation.
Review
Biochemistry & Molecular Biology
Tuane C. R. G. Vieira, Caroline A. Barros, Renato Domingues, Tiago Fleming Outeiro
Summary: The discovery of prions challenges dogmas and revolutionizes our understanding of protein-misfolding diseases. The concept of self-propagation via protein conformational changes applies to other proteins, such as alpha-synuclein, in Parkinson's disease and other synucleinopathies. The transfer of alpha-synuclein between cells may involve receptor-mediated transport, with the cellular prion protein playing a crucial role. Understanding the interaction between alpha-synuclein and the cellular prion protein is important for synucleinopathies.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Veterinary Sciences
Erez Harpaz, Tram Thu Vuong, Linh Tran, Michael Andreas Tranulis, Sylvie L. Benestad, Cecilie Ersdal
Summary: This study used serial protein misfolding cyclic amplification to investigate the conversion ability of prion isolates from reindeer, red deer, and moose, as well as experimental classical scrapie from sheep, in various species. The results showed that reindeer CWD isolate successfully converted substrates from all tested species except goats, while the red deer isolate failed to convert sheep and goat substrates but exhibited amplification in all cervid substrates. The moose isolates had lower conversion efficacies. The experimental classical scrapie isolate was successfully propagated in substrates from all tested species. This suggests the potential for spillover of reindeer CWD and classical sheep scrapie to different species, and the vulnerability of roe deer to prion disease.
VETERINARY RESEARCH
(2023)
Review
Virology
Sandra Pritzkow
Summary: Chronic wasting disease (CWD) is a prion disease that affects multiple species of cervids, and its uncontrolled spread in North America in the last few decades has posed risks to the environment, animals, and potentially humans. This review discusses the mechanisms and routes of CWD transmission, strain diversity, spillover and zoonotic potential, as well as strategies to minimize the threat of CWD.
Review
Cell Biology
Daniel Shoup, Suzette A. Priola
Summary: Through in vivo and in vitro assays, this study investigates the interactions between different prion strains and cell types and their contributions to prion disease pathology. The findings suggest a balance between prion propagation and degradation in cellular infection, which can be influenced by different cell lines.
CELL AND TISSUE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Simote T. Foliaki, Aleksandar Wood, Katie Williams, Anna Smith, Ryan O. Walters, Chase Baune, Bradley R. Groveman, Cathryn L. Haigh
Summary: Cellular prion protein (PrPC) protects neurons against oxidative stress damage and plays a crucial role in network communication and cytoskeleton protection. The loss of PrPC function is associated with the development of prion diseases. The study found that PrPC has a neuroprotective role in oxidative stress damage, and its GPI anchoring structure is required for the recovery of damage.
Article
Neurosciences
Pingping Shen, Johnny Dang, Zerui Wang, Weiguanliu Zhang, Jue Yuan, Yue Lang, Mingxuan Ding, Marcus Mitchell, Qingzhong Kong, Jiachun Feng, Annemiek J. M. Rozemuller, Li Cui, Robert B. Petersen, Wen-Quan Zou
Summary: The research revealed that PrP(Sc) in the brain of the GSS patient is predominantly composed of the mutant PrP(Q227X), incapable of recruiting the wild-type PrP(Wt) in vivo but successful in recruiting from transgenic mice. Cellular analysis showed that the mutant PrP(Q227X) is mainly present in the cell culture medium, while the wild-type PrP(Wt) is mostly found in the cell lysate.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Luis Concha-Marambio, Fei Wang, Enrique Armijo, Damian Gorski, Frank Ramirez, Andrew Scowcroft, Sandra Pritzkow, Claudio Soto
Summary: In this article, the authors describe a method for rapid and efficient generation of large quantities of highly infectious prions using the Protein Misfolding Cyclic Amplification (PMCA) technology. They also developed a bioreactor format that can continuously produce PrPSc without the need to add brain-derived prions. The LS-PMCA technology has been shown to work with various species and strains of prions, making it a valuable tool for biological and structural studies.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Diane L. Ritchie, Marcelo A. Barria
Summary: Accumulation and propagation of misfolded proteins in the brain are shared pathological features of many neurodegenerative diseases. While there is no epidemiological evidence suggesting infectiousness in neurodegenerative disorders, experimental models show potential prion-like transmission of other pathogenic proteins. Concerns exist regarding the transmission of misfolded proteins beyond prion protein.
Article
Biochemistry & Molecular Biology
Korina Karagianni, Spyros Pettas, Eirini Kanata, Elisavet Lioulia, Katrin Thune, Matthias Schmitz, Ioannis Tsamesidis, Evgenia Lymperaki, Konstantinos Xanthopoulos, Theodoros Sklaviadis, Dimitra Dafou
Summary: The catechol-type diterpene Carnosic acid (CA) and its metabolite Carnosol (CS) from Rosmarinus officinalis have antioxidant and neuroprotective effects, reducing the accumulation and disrupting the aggregation of disease-associated PrP in prion diseases.
Article
Biochemistry & Molecular Biology
Itzik Cooper, Katayun Cohen-Kashi Malina, Yishai Levin, Alexandra Gabashvili, Boaz Mohar, Alfredo Cagnotto, Mario Salmona, Vivian Teichberg
Summary: This study investigated the mechanisms of interaction between PrP 106-126 and the blood-brain barrier (BBB). It was found that PrP 106-126 treatment reduced BBB function, decreased cAMP levels, increased nitric oxide (NO) levels, and altered the activation modes of the GTPases Rac1 and RhoA. Proteomic analysis revealed significant changes in cytoskeleton-related protein expression. These findings highlight the nature of the interaction between PrP 106-126 and the BBB, and underscore the importance of the cytoskeleton in endothelial response to prion-induced stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Francesca De Giorgi, Vladimir N. Uversky, Francois Ichas
Summary: The article discusses Lionel Penrose's invention of the first self-replicating mechanical device in 1957 and its function, as well as its relevance to the genesis and proliferation of amyloid fibrils. It also highlights the significance of studies on alpha-Synuclein and its similarities to prions, its fibrillization-prone domain, and its nature as an intrinsically disordered protein. Combining these discoveries with the concept of the Penrose machine, the article proposes an explanation for the emergence and spread of different alpha-Synuclein fibril strains in alpha-Synucleinopathies.
Article
Neurosciences
Rajesh Kushwaha, Yue Li, Natallia Makarava, Narayan P. Pandit, Kara Molesworth, Konstantin G. Birukov, Ilia V. Baskakov
Summary: This study is the first to demonstrate early breakdown of the blood-brain barrier in prion disease and to show that reactive astrocytes associated with prion disease are detrimental to BBB integrity. The harmful effects are linked to proinflammatory factors secreted by reactive astrocytes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Alba Marin-Moreno, Juan Carlos Espinosa, Patricia Aguilar-Calvo, Natalia Fernandez-Borges, Jose Luis Pitarch, Lorenzo Gonzalez, Juan Maria Torres
Summary: The protective role of the E/D-163 polymorphism of dog prion protein against prion replication may not be the sole factor for canid prion resistance, as other PrP residues or factors distinct than PrP may participate in this process. Different factors may be required for D-162 sheep PrP to effectively protect sheep against ruminant prions, as observed through inoculation of various prion strains in a transgenic mouse model expressing different PrP variants.
SCIENTIFIC REPORTS
(2021)
Article
Pathology
Enric Vidal, Carlos Lopez-Figueroa, Jordi Rodon, Monica Perez, Marco Brustolin, Guillermo Cantero, Victor Guallar, Nuria Izquierdo-Useros, Jorge Carrillo, Julia Blanco, Bonaventura Clotet, Julia Vergara-Alert, Joaquim Segales
Summary: This study chronologically characterized the neuroinvasion and neuropathology of SARS-CoV-2 in a mouse model. The virus was found to enter the brain early through the olfactory mucosa and rapidly spread between neurons, causing acute encephalitis and neuronal damage.
VETERINARY PATHOLOGY
(2022)
Article
Microbiology
Enric Vidal, Judit Burgaya, Lorraine Michelet, Claudia Arrieta-Villegas, Guillermo Cantero, Krystel de Cruz, Jennifer Tambosco, Michelle Di Bari, Romolo Nonno, Maria Laura Boschiroli, Bernat Perez de Val
Summary: A laboratory infection model was established to reproduce Mycobacterium microti infection in bank voles, successfully mimicking the disease phenotype observed in free-ranging voles. The pathogenesis of the infection was characterized, with most voles showing multifocal and diffuse granulomatous lesions in the liver and spleen. Mycobacterial DNA was detected in feces but not in oral swabs, suggesting horizontal transmission between voles.
Article
Clinical Neurology
Hasier Erana, Beatriz San Millan, Carlos M. Diaz-Dominguez, Jorge M. Charco, Rosa Rodriguez, Irene Vieitez, Arrate Pereda, Rosa Yanez, Marivi Geijo, Carmen Navarro, Guiomar Perez de Nanclares, Susana Teijeira, Joaquin Castilla
Summary: Gerstmann-Straussler-Scheinker disease (GSS) is a rare neurodegenerative illness caused by pathogenic alterations in the prion protein (PrP) coding gene, leading to the formation of toxic prions and showing variability in clinical and neuropathological manifestations.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Matthias Schmitz, Sezgi Canaslan, Juan Carlos Espinosa, Natalia Fernandez-Borges, Anna Villar-Pique, Franc Llorens, Daniela Varges, Fabian Maass, Juan Maria Torres, Peter Hermann, Inga Zerr
Summary: Biomarkers, specifically neurofilament light chain (NfL), have shown potential as stable and accurate markers for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). This study confirms the stability and consistency of CSF and plasma NfL levels in a large cohort of sCJD patients. The newly defined cutoffs for NfL offer good diagnostic accuracies in distinguishing sCJD from control groups. Additionally, the study suggests that NfL could be used as a very early biomarker for sCJD diagnosis.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Microbiology
Alicia Otero, Tomas Barrio, Hasier Erana, Jorge M. Charco, Marina Betancor, Carlos M. Diaz-Dominguez, Belen Marin, Olivier Andreoletti, Juan M. Torres, Qingzhong Kong, Juan J. Badiola, Rosa Bolea, Joaquin Castilla
Summary: In this study, the effect of glycosylation on the characteristics of BSE isolates was assessed using a non-glycosylated human PrPC-expressing mouse model. The findings showed that BSE prions could be propagated in a non-glycosylated human PrPC environment without losing their strain properties. BSE prions transmitted to the transgenic mouse model exhibited neuropathological and biochemical signs compatible with BSE, confirming that the glycosylation of human PrPC is not essential for the propagation of this particular prion strain.
Article
Biochemistry & Molecular Biology
Ilaria Vanni, Floriana Iacobone, Claudia D'Agostino, Matteo Giovannelli, Laura Pirisinu, Hermann Clemens Altmeppen, Joaquin Castilla, Juan Maria Torres, Umberto Agrimi, Romolo Nonno
Summary: The PrPC protein undergoes various endoproteolytic events, resulting in bioactive fragments with physiological functions and implications in neurodegenerative diseases. Lack of methods to identify all PrPC-derived proteoforms has hindered comprehensive investigations. Researchers developed an optimized Western blot assay based on previous knowledge, enabling the identification of the full spectrum of PrPC proteoforms in brain samples.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Clinical Neurology
Izaro Kortazar-Zubizarreta, Hasier Erana, Arrate Pereda, Jorge M. Charco, Africa Manero-Azua, Rebeca Ruiz-Onandi, Urko Aguirre, Gonzalo Gonzalez-Chinchon, Guiomar Perez de Nanclares, Joaquin Castilla
Summary: This study provides detailed data on clinical, diagnostic, histopathological, and biochemical characteristics of a recent series of fatal familial insomnia (FFI) cases. The series includes 16 patients, with 25% lacking family history, and highlights the highest diagnostic value of polysomnography and genetic study in FFI. The study also identifies key histopathological findings and compares the effectiveness of different tests for FFI diagnosis, such as Western blotting and RT-QuIC.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Neurosciences
Enric Vidal, Manuel A. Sanchez-Martin, Hasier Erana, Sonia Perez Lazaro, Miguel A. Perez-Castro, Alicia Otero, Jorge M. Charco, Belen Marin, Rafael Lopez-Moreno, Carlos M. Diaz-Dominguez, Marivi Geijo, Montserrat Ordonez, Guillermo Cantero, Michele di Bari, Nuria L. Lorenzo, Laura Pirisinu, Claudia d'Agostino, Juan Maria Torres, Vincent Beringue, Glenn Telling, Juan J. Badiola, Marti Pumarola, Rosa Bolea, Romolo Nonno, Jesus R. Requena, Joaquin Castilla
Summary: Atypical Scrapie is considered a spontaneous idiopathic prion disease in small ruminants, and unlike classical scrapie, its occurrence and control strategies may affect its transmissibility.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Ecology
Enric Vidal, Johan Espunyes, Maria Puig Ribas, Cristian Melgarejo, Laura Martino, Lorraine Michelet, Maria Laura Boschiroli, Albert Sanz, Alberto Allepuz, Oscar Cabezon, Bernat Perez de Val
Summary: A study in the Catalan Pyrenees revealed that wild small rodents did not play a role in the epidemiology of M. microti outbreak in the area. The source of this mycobacterium remains unknown, but the movements of wild boars across the French Pyrenees are considered the most likely origin of the outbreak detected in the Iberian Peninsula.
EUROPEAN JOURNAL OF WILDLIFE RESEARCH
(2023)
Article
Agriculture, Dairy & Animal Science
E. Ruiz-Riera, E. Vidal, A. Canturri, A. Lehmbecker, M. Cuvertoret, C. Lopez-Figueroa, W. Baumgaertner, M. Domingo, J. Segales
Summary: This study describes a new pathological condition in pigs, characterized by wasting and vacuolization of the brain. The affected and healthy pigs from eight farms were investigated, and the most consistent lesion observed was neuropil vacuolization in the forebrain. Supplementation with nutritional complexes improved the condition, suggesting a metabolic origin.
Review
Biochemistry & Molecular Biology
Alba Marin-Moreno, Sara Canoyra, Natalia Fernandez-Borges, Juan Carlos Espinosa, Juan Maria Torres
Summary: Neurodegenerative diseases are a major health challenge that modern medicine and advanced societies are facing. Despite years of research, the exact mechanisms leading to neuronal death and effective treatments have not been fully understood. The use of animal models, particularly transgenic mouse models, has provided valuable insights into the pathology of neurodegenerative diseases and the search for potential therapies.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Microbiology
Carlos Neila-Ibanez, Ester Pintado, Roser Velarde, Xavier Fernandez Aguilar, Enric Vidal, Virginia Aragon, M. Lourdes Abarca
Summary: The study provides information on lesions caused by Streptococcus ruminantium in Pyrenean chamois and domestic sheep, as well as details about the phenotypic biopatterns and antimicrobial resistance of the isolates.
MICROBIOLOGY RESEARCH
(2022)