scholarly journals Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation

2013 ◽  
Vol 126 (1) ◽  
pp. 131-144 ◽  
Author(s):  
Therese Fagerqvist ◽  
Veronica Lindström ◽  
Eva Nordström ◽  
Anna Lord ◽  
Stina M. E. Tucker ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Lewy Body ◽  
Brain Pathology ◽  
A30p Mutation

scholarly journals Preclinical Detection of Alpha-Synuclein Seeding Activity in the Colon of a Transgenic Mouse Model of Synucleinopathy by RT-QuIC

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 759
Author(s):  
Jung-Youn Han ◽  
Chaewon Shin ◽  
Young Pyo Choi
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Lewy Body ◽  
Dementia With Lewy Body ◽  
Transgenic Mouse Model ◽  
Alpha Synuclein ◽  
Gi Tract ◽  
Colon Tissue ◽  
Presymptomatic Stage ◽  
The Brain

In synucleinopathies such as Parkinson’s disease (PD) and dementia with Lewy body (DLB), pathological alpha-synuclein (α-syn) aggregates are found in the gastrointestinal (GI) tract as well as in the brain. In this study, using real-time quaking-induced conversion (RT-QuIC), we investigated the presence of α-syn seeding activity in the brain and colon tissue of G2-3 transgenic mice expressing human A53T α-syn. Here we show that pathological α-syn aggregates with seeding activity were present in the colon of G2-3 mice as early as 3 months old, which is in the presymptomatic stage prior to the observation of any neurological abnormalities. In contrast, α-syn seeding activity was not detectable in 3 month-old mouse brains and only identified at 6 months of age in one of three mice. In the symptomatic stage of 12 months of age, RT-QuIC seeding activity was consistently detectable in both the brain and colon of G2-3 mice. Our results indicate that the RT-QuIC assay can presymptomatically detect pathological α-syn aggregates in the colon of G2-3 mice several months prior to their detection in brain tissue.

scholarly journals Generation and Characterization of Novel Monoclonal Antibodies Targeting p62/sequestosome-1 Across Human Neurodegenerative Diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 407-418
Author(s):  
Jorge A Trejo-Lopez ◽  
Zachary A Sorrentino ◽  
Cara J Riffe ◽  
Stefan Prokop ◽  
Dennis W Dickson ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Alzheimer Disease ◽  
Neurodegenerative Diseases ◽  
Progressive Supranuclear Palsy ◽  
Lewy Body ◽  
Lewy Body Disease ◽  
Ubiquitin Proteasome System ◽  
Lewy Neurites ◽  
Sequestosome 1 ◽  
Cellular Autophagy

Abstract Human neurodegenerative diseases can be characterized as disorders of protein aggregation. As a key player in cellular autophagy and the ubiquitin proteasome system, p62 may represent an effective immunohistochemical target, as well as mechanistic operator, across neurodegenerative proteinopathies. In this study, 2 novel mouse-derived monoclonal antibodies 5G3 and 2A5 raised against residues 360–380 of human p62/sequestosome-1 were characterized via immunohistochemical application upon human tissues derived from cases of C9orf72-expansion spectrum diseases, Alzheimer disease, progressive supranuclear palsy, Lewy body disease, and multiple system atrophy. 5G3 and 2A5 reliably highlighted neuronal dipeptide repeat, tau, and α-synuclein inclusions in a distribution similar to a polyclonal antibody to p62, phospho-tau antibodies 7F2 and AT8, and phospho-α-synuclein antibody 81A. However, antibodies 5G3 and 2A5 consistently stained less neuropil structures, such as tau neuropil threads and Lewy neurites, while 2A5 marked fewer glial inclusions in progressive supranuclear palsy. Both 5G3 and 2A5 revealed incidental astrocytic tau immunoreactivity in cases of Alzheimer disease and Lewy body disease with resolution superior to 7F2. Through their unique ability to highlight specific types of pathological deposits in neurodegenerative brain tissue, these novel monoclonal p62 antibodies may provide utility in both research and diagnostic efforts.

O1-06-05: Monoclonal antibodies selective for Aβ protofibrils reduce plaque burden in transgenic mice models of Alzheimer's disease

2006 ◽  
Vol 2 ◽  
pp. S21-S21
Author(s):  
Lars Lannfelt ◽  
Dag Sehlin ◽  
Hillevi Englund ◽  
Anna Lord ◽  
Ann-Sofi Johansson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Plaque Burden

scholarly journals Human Monoclonal Antibodies againstPseudomonas aeruginosa Lipopolysaccharide Derived from Transgenic Mice Containing Megabase Human Immunoglobulin Loci Are Opsonic and Protective against Fatal Pseudomonas Sepsis

2001 ◽  
Vol 69 (4) ◽  
pp. 2223-2229 ◽  
Author(s):  
Sonali Hemachandra ◽  
Kulwant Kamboj ◽  
Janna Copfer ◽  
Gerald Pier ◽  
Larry L. Green ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Variable Region ◽  
Human Immunoglobulin ◽  
High Avidity ◽  
Genes Encoding ◽  
Antibody Titers ◽  
Multiple Donors ◽  
Human Polymorphonuclear Leukocytes ◽  
Variable Region Genes

ABSTRACT Pseudomonas aeruginosa is a significant human pathogen, and no vaccine is commercially available. Passive antibody prophylaxis using monoclonal antibodies (MAb) against protectiveP. aeruginosa epitopes is an alternative strategy for preventing P. aeruginosa infection, but mouse MAb are not suitable for use in humans. Polyclonal human antibodies from multiple donors have variable antibody titers, and human MAb are difficult to make. We used immunoglobulin-inactivated transgenic mice reconstituted with megabase-size human immunoglobulin loci to generate a human MAb against the polysaccharide (PS) portion of the lipopolysaccharide O side chain of a common pathogenic serogroup ofP. aeruginosa, 06ad. The anti-PS human immunoglobulin G2 MAb made from mice immunized with heat-killed P. aeruginosa was specific for serogroup 06ad pseudomonas. The MAb was highly opsonic for the uptake and killing of P. aeruginosa by human polymorphonuclear leukocytes in the presence of human complement. In addition, 25 μg of the MAb protected 100% of neutropenic mice from fatal P. aeruginosasepsis. DNA sequence analysis of the genes encoding the MAb revealed VH3 and Vκ2/A2 variable-region genes, similar to variable-region genes in humans immunized with bacterial PS and associated with high-avidity anti-PS antibodies. We conclude that human MAb to P. aeruginosa made in these transgenic mice are highly protective and that these mice mimic the antibody response seen in humans immunized with T-cell-independent antigens such as bacterial PS.

The diversity of antigen-specific monoclonal antibodies from transgenic mice bearing human immunoglobulin gene miniloci

1994 ◽  
Vol 24 (11) ◽  
pp. 2672-2681 ◽  
Author(s):  
Simon D. Wagner ◽  
Andrei V. Popov ◽  
Sarah L. Davies ◽  
Jian Xian ◽  
Michael S. Neuberger ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Human Immunoglobulin ◽  
Immunoglobulin Gene

scholarly journals Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody

2020 ◽  
Author(s):  
Ronit Rosenfeld ◽  
Tal Noy-Porat ◽  
Adva Mechaly ◽  
Efi Makdasi ◽  
Yinon Levy ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Human Monoclonal Antibody ◽  
Human Monoclonal Antibodies ◽  
Mortality And Morbidity ◽  
Life Saving ◽  
Therapeutic Value

AbstractCoronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human live, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterized and further evaluated the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. 75% of the untreated mice succumbed 6-9 days post-infection while administration of the MD65 antibody as late as 3 days after exposure, rescued all infected animals. The data unprecedentedly demonstrate, the therapeutic value of human monoclonal antibodies as a life-saving treatment of severe COVID-19 infection.

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