Review
Cell Biology
Robert C. C. Mercer, David A. Harris
Summary: This review provides current knowledge on the neurotoxic mechanisms of prion diseases, including the functions of PrPC, its interactions with other extracellular proteins, in vivo and in vitro models, and the role of non-neuronal cell types in pathogenesis.
CELL AND TISSUE RESEARCH
(2023)
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)
Review
Neurosciences
Stefano Thellung, Alessandro Corsaro, Irene Dellacasagrande, Mario Nizzari, Martina Zambito, Tullio Florio
Summary: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are progressive neurodegenerative disorders that affect humans and animals. Current treatments for these diseases are ineffective. The misfolding of prion protein is a key factor in the pathogenesis of TSEs, and alterations in protein homeostasis worsen the severity of the disease. Restoring protein homeostasis pathways through pharmacological interventions may help reduce the burden of misfolded prion protein and improve the condition of patients.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Virology
Sonia M. Vallabh, Dan Zou, Rose Pitstick, Jill O'Moore, Janet Peters, Derek Silvius, Jasna Kriz, Walker S. Jackson, George A. Carlson, Eric Vallabh Minikel, Deborah E. Cabin
Summary: There is an urgent need to develop drugs for prion disease, and the choice of animal models to support drug development programs is a subject of debate. This study tested the efficacy of the small molecule anle138b in multiple mouse models of prion disease. The results showed that anle138b doubled the survival of mice infected with the RML strain of prions and suppressed astrogliosis. However, in mouse models with genetic prion disease, it was challenging to identify a clear disease endpoint to measure therapeutic efficacy.
JOURNAL OF VIROLOGY
(2023)
Article
Neurosciences
Marina Betancor, Laura Moreno-Martinez, Oscar Lopez-Perez, Alicia Otero, Adelaida Hernaiz, Tomas Barrio, Juan Jose Badiola, Rosario Osta, Rosa Bolea, Inmaculada Martin-Burriel
Summary: TTC, as a neuroprotective molecule, shows significant neuroprotective effects in murine models of prion diseases, reducing apoptosis, regulating autophagy, and increasing neuronal survival, although it does not extend survival time in these models.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Bryan A. Killinger, Lee L. Marshall, Diptaman Chatterjee, Yaping Chu, Jose Bras, Rita Guerreiro, Jeffrey H. Kordower
Summary: This study used biotinylation by antibody recognition (BAR) to label pathological alpha-synuclein and performed mass spectrometry analysis on Lewy pathology (LP). It identified 261 enriched proteins in synucleinopathy brains and revealed PD as the most significant pathway. BAR has the potential to help understand LP in primary human tissue and animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Yeong-Gon Choi, Byungki Jang, Jeong-Ho Park, Min-Woo Choi, Gong Yeal Lee, Dae Jin Cho, Hong Youp Kim, Hae Kyoung Lim, Won Jae Lee, Eun-Kyoung Choi, Yong-Sun Kim
Summary: Conversion of PrPC into PrPSc and PRNP mutations are definite causes of prion diseases, which are untreatable and fatal. This study investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib in prion models and found that it inhibited PrPSc deposition and improved survival time in hamsters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Ines C. Bras, Tiago F. Outeiro
Summary: Accumulation of misfolded alpha-synuclein (aSyn) in the brain is central to Parkinson's disease (PD) pathogenesis, with cell-to-cell transmission leading to the stereotypical distribution and evolution of pathology forming synucleinopathies. While progress has been made, mechanisms involved in the transfer of aSyn assemblies and their role in driving PD progression remain unclear.
Review
Biochemistry & Molecular Biology
Timothy Sampson
Summary: Microbial amyloids are associated with neurodegenerative diseases and may contribute to amyloid pathologies through interactions with host amyloid proteins.
Article
Clinical Neurology
Regina R. Reimann, Martina Puzio, Antonella Rosati, Marc Emmenegger, Bernard L. Schneider, Pamela Valdes, Danzhi Huang, Amedeo Caflisch, Adriano Aguzzi
Summary: The cellular prion protein PrPC mediates neurotoxicity of prions and protein aggregates, but the mechanisms are not well understood. Antibody-derived ligands against PrPC induce neurotoxicity through hydrogen bonding and suppressing this bond prolongs the lives of prion-infected mice, suggesting convergent pathways. A study found that the toxic effects of these ligands require a specific amino acid residue within PrPC, which could be a potential target for preventing prion-related neurodegeneration.
Article
Multidisciplinary Sciences
Julie-Myrtille Bourgognon, Jereme G. Spiers, Sue W. Robinson, Hannah Scheiblich, Paul Glynn, Catharine Ortori, Sophie J. Bradley, Andrew B. Tobin, Joern R. Steinert
Summary: The study demonstrated that pharmacological suppression of neuroinflammatory NO signaling could slow down neurodegenerative disease progression and reduce cellular stress associated with nitrosation and protein misfolding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Marina Betancor, Sonia Perez-Lazaro, Alicia Otero, Belen Marin, Inmaculada Martin-Burriel, Kaj Blennow, Juan Jose Badiola, Henrik Zetterberg, Rosa Bolea
Summary: This study evaluated the changes of neurogranin (Ng) and neurofilament light chain (NfL) at both protein and gene expression levels in the central nervous system (CNS) of preclinical and clinical scrapie-affected sheep. The levels of Ng and NfL decreased as the disease progressed, while the concentrations of NfL in cerebrospinal fluid (CSF) increased. These proteins may serve as biomarkers for neurodegeneration in preclinical cases of scrapie.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Asad Jan, Nadia Pereira Goncalves, Christian Bjerggaard Vaegter, Poul Henning Jensen, Nelson Ferreira
Summary: The pathological aggregation of presynaptic protein alpha-synuclein and its propagation through synaptically coupled neuroanatomical tracts are believed to underlie the progression of Parkinson's disease and other synucleinopathies. Understanding the mechanisms of alpha-synuclein propagation may provide insights into the etiology of PD and identify new therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Asvin K. K. Lakkaraju, Karl Frontzek, Emina Lemes, Uli Herrmann, Marco Losa, Rajlakshmi Marpakwar, Adriano Aguzzi
Summary: This study found that prion infection and prion-mimetic antibodies deplete PIKfyve, a phosphoinositide kinase controlling endolysosomal maturation, leading to endolysosomal hypertrophy and activation of lysosomal enzymes. This depletion of PIKfyve is mediated by acyltransferases zDHHC9 and zDHHC21, whose topology is disturbed by prion infection, resulting in vacuolation in prion diseases. Restoring PIKfyve levels through different methods can suppress prion-induced vacuolation and restore lysosomal homeostasis.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Mo-Jong Kim, Hee-Jun Kim, Byungki Jang, Hyun-Ji Kim, Mohd Najib Mostafa, Seok-Joo Park, Yong-Sun Kim, Eun-Kyoung Choi
Summary: Mitochondrial dynamics and quality control play a crucial role in cell survival and bioenergetics. However, aberrant mitochondrial quality control has been implicated in various human diseases, including neurological disorders like prion disease. This study investigated the involvement of mitochondrial quality control in prion pathogenesis and found that scrapie infection led to mitochondrial dysfunction through impaired mitochondrial quality control processes, ultimately resulting in neuronal cell death.
Article
Immunology
Mars Stone, Clara Di Germanio, David J. Wright, Hasan Sulaeman, Honey Dave, Rebecca Fink, Edward P. Notari, Valerie Green, Donna Strauss, Debbie Kessler, Mark Destree, Paula Saa, Phillip C. Williamson, Graham Simmons, Susan L. Stramer, Jean Opsomer, Jefferson M. Jones, Steven Kleinman, Michael P. Busch
Summary: This study conducted seroprevalence testing for SARS-CoV-2 antibodies in blood donors from 6 US metropolitan regions. The results showed an increase in seroprevalence over time, with the largest increase in New York. Seroprevalence was higher in younger, non-Hispanic black, and Hispanic donors, and correlated with regional case rates.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Medicine, General & Internal
Jefferson M. Jones, Mars Stone, Hasan Sulaeman, Rebecca Fink, Honey Dave, Matthew E. Levy, Clara Di Germanio, Valerie Green, Edward Notari, Paula Saa, Brad J. Biggerstaff, Donna Strauss, Debra Kessler, Ralph Vassallo, Rita Reik, Susan Rossmann, Mark Destree, Kim-Anh Nguyen, Merlyn Sayers, Chris Lough, Daniel W. Bougie, Megan Ritter, Gerardo Latoni, Billy Weales, Stacy Sime, Jed Gorlin, Nicole E. Brown, Carolyn Gould, Kevin Berney, Tina J. Benoit, Maureen J. Miller, Dane Freeman, Deeksha Kartik, Alicia M. Fry, Eduardo Azziz-Baumgartner, Aron J. Hall, Adam MacNeil, Adi Gundlapalli, Sridhar Basavaraju, Susan Gerber, Monica E. Patton, Brian Custer, Phillip Williamson, Graham Simmons, Natalie J. Thornburg, Steven Kleinman, Susan L. Stramer, Jean Opsomer, Michael P. Busch
Summary: A study based on blood donations in the US from July 2020 to May 2021 found that seroprevalence of SARS-CoV-2 antibodies induced by vaccination or infection increased over time and varied by age, race and ethnicity, and geographic region. Despite adjustments for demographic differences, the findings may not be fully representative of the entire US population.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2021)
Article
Hematology
Sonia Bakkour, Paula Saa, Jamel A. Groves, Leilani Montalvo, Clara Di Germanio, Sonja M. Best, Eduard Grebe, Kristin Livezey, Jeffrey M. Linnen, Donna Strauss, Debra Kessler, Mark Bonn, Valerie Green, Phillip Williamson, Steve Kleinman, Susan L. Stramer, Mars Stone, Michael P. Busch
Summary: The study examined SARS-CoV-2 RNAemia prevalence in blood donors from six areas in the United States, showing that it is infrequent and at low concentrations when detected. Only one reactive sample was tested for infectivity and was found to be non-infectious in cell culture, supporting the current recommendations against screening donors by NAT.
Review
Hematology
Roger Y. Dodd, Bryan R. Spencer, Meng Xu, Gregory A. Foster, Paula Saa, Jaye P. Brodsky, Susan L. Stramer
Summary: In the United States, blood collection organizations tested all blood donors for antibodies to SARS-CoV-2 to increase donations and identify potential COVID-19 convalescent plasma donors. The overall seroreactivity among blood donors was 4.22%, with the highest rates in the Midwest region. Younger donors aged 18-24, African-Americans, and Hispanics had higher seroreactivity rates.
TRANSFUSION MEDICINE REVIEWS
(2021)
Article
Immunology
Roger Y. Dodd, Edward P. Notari, Jaye P. Brodsky, Gregory A. Foster, Meng Xu, Paula Saa, Susan L. Stramer
Summary: The study found that the rapid increase in prevalence of SARS-CoV-2 antibodies was largely due to vaccination. Among donors who reported vaccination, the majority (86.84%) were reactive to S1 antibodies only in response to vaccination, while among those who did not report vaccination, 25.07% had reactivity to both antibodies.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Hematology
Rebecca Fink, Lois Fisher, Hasan Sulaeman, Honey Dave, Matthew E. Levy, Lily McCann, Clara Di Germanio, Edward P. Notari, Valerie Green, Sherri Cyrus, Phillip Williamson, Paula Saa, James M. Haynes, Jamel Groves, Sunitha Mathew, Zhanna Kaidarova, Roberta Bruhn, Eduard Grebe, Jean Opsomer, Jefferson M. Jones, Maureen J. Miller, Michael P. Busch, Mars Stone
Summary: A national serosurvey of U.S. blood donors was conducted to estimate the prevalence of SARS-CoV-2 infections and vaccinations. The study collaborated with multiple organizations and government partners to test and analyze blood donation specimens. The results were made available to public health professionals and the general public, highlighting the role of the blood collection industry in public-private partnerships during a public health emergency.
Article
Immunology
Michael P. Busch, Susan L. Stramer, Mars Stone, Elaine A. Yu, Eduard Grebe, Edward Notari, Paula Saa, Robyn Ferg, Irene Molina Manrique, Natalia Weil, Rebecca Fink, Matthew E. Levy, Valerie Green, Sherri Cyrus, Phillip C. Williamson, James Haynes, Jamel Groves, David Krysztof, Brian Custer, Steve Kleinman, Brad J. Biggerstaff, Jean D. Opsomer, Jefferson M. Jones
Summary: Substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity were observed in the US in 2021.
CLINICAL INFECTIOUS DISEASES
(2022)
Review
Cell Biology
Robert C. C. Mercer, David A. Harris
Summary: This review provides current knowledge on the neurotoxic mechanisms of prion diseases, including the functions of PrPC, its interactions with other extracellular proteins, in vivo and in vitro models, and the role of non-neuronal cell types in pathogenesis.
CELL AND TISSUE RESEARCH
(2023)
Article
Immunology
Laura Tonnetti, Roger Y. Dodd, Donna D. Burke, Paula Saa, Bryan R. Spencer, Meng Xu, James M. Haynes, Susan L. Stramer
Summary: This study monitored the antibody levels of 249 blood donors for 18 months, and found that the majority of vaccinated donors remained asymptomatic and noninfected, while approximately two thirds of infected donors reported symptoms. The levels of antibodies showed different trends over the 18-month period, with a significant increase in anti-S1 levels after vaccination or booster shots (hybrid immunity) and a gradual decrease in anti-N levels.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Immunology
Paula Saa, Rebecca Fink, Hina Dawar, Clara Di Germanio, Leilani Montalvo, David J. Wright, David E. Krysztof, Steven H. Kleinman, Theresa Nester, Debra A. Kessler, Rebecca L. Townsend, Bryan R. Spencer, Hany Kamel, Jackie Vannoy, Michael P. Busch, Susan L. Stramer, Mars Stone, Philip J. Norris
Summary: Presymptomatic plasma samples from 1596 donors with a history of Covid-19 infection or symptoms were tested for SARS-CoV-2 RNA and antibodies. Prior infection and vaccination provided protection against RNAemia and symptomatic infection. No difference in RNAemia rates was observed between the Delta and Omicron variant eras.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Public, Environmental & Occupational Health
Jefferson M. Jones, Irene Molina Manrique, Mars S. Stone, Eduard Grebe, Paula Saa, Clara D. Germanio, Bryan R. Spencer, Edward Notari, Marjorie Bravo, Marion C. Lanteri, Valerie Green, Melissa Briggs-Hagen, Melissa M. Coughlin, Susan L. Stramer, Jean Opsomer, Michael P. Busch
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
(2023)
Article
Public, Environmental & Occupational Health
Jefferson M. Jones, Irene Molina Manrique, Mars S. Stone, Eduard Grebe, Paula Saa, Clara D. Germanio, Bryan R. Spencer, Edward Notari, Marjorie Bravo, Marion C. Lanteri, Valerie Green, Melissa Briggs-Hagen, Melissa M. Coughlin, Susan L. Stramer, Jean Opsomer, Michael P. Busch
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
(2023)
Article
Medicine, Research & Experimental
Paula Saa, Rebecca V. Fink, Sonia Bakkour, Jing Jin, Graham Simmons, Marcus O. Muench, Hina Dawar, Clara Di Germanio, Alvin J. Hui, David J. Wright, David E. Krysztof, Steven H. Kleinman, Angela Cheung, Theresa Nester, Debra A. Kessler, Rebecca L. Townsend, Bryan R. Spencer, Hany Kamel, Jacquelyn M. Vannoy, Honey Dave, Michael P. Busch, Susan L. Stramer, Mars Stone, Rachael P. Jackman, Philip J. Norris
Summary: Unlike respiratory viruses such as influenza, SARS-CoV-2 can be detected in the blood of COVID-19 patients. Reports of COVID-19 symptoms or diagnosis after blood donation were associated with increased mortality in the general population. The detection rate of RNAemia in blood donors with possible COVID-19-related post-donation information (PDI) reached 9%-15% in late 2020 to early 2021 and decreased to approximately 4% after widespread vaccination. Donors with RNAemia were more likely to report cough, shortness of breath, change in taste, or smell compared to infected donors without detectable RNAemia. No infectious virus was found in plasma samples, indicating a minimal risk of transmitting SARS-CoV-2 through blood transfusions.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Hematology
Sonia Bakkour, Paula Saa, Rebecca Townsend, Honey Dave, Debra A. Kessler, Jackie Vannoy, Steven Kleinman, Mars Stone, Susan L. Stramer, Philip J. Norris
Meeting Abstract
Hematology
Bryan R. Spencer, Roger Y. Dodd, Gregory A. Foster, Laura Tonnetti, Paula Saa, Susan L. Stramer
