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Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against...

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Autores principales: Masliah, Eliezer, Rockenstein, Edward, Mante, Michael, Crews, Leslie, Spencer, Brian, Adame, Anthony, Patrick, Christina, Trejo, Margarita, Ubhi, Kiren, Rohn, Troy T., Mueller-Steiner, Sarah, Seubert, Peter, Barbour, Robin, McConlogue, Lisa, Buttini, Manuel, Games, Dora, Schenk, Dale
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084838/
https://www.ncbi.nlm.nih.gov/pubmed/21559417
http://dx.doi.org/10.1371/journal.pone.0019338
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author Masliah, Eliezer
Rockenstein, Edward
Mante, Michael
Crews, Leslie
Spencer, Brian
Adame, Anthony
Patrick, Christina
Trejo, Margarita
Ubhi, Kiren
Rohn, Troy T.
Mueller-Steiner, Sarah
Seubert, Peter
Barbour, Robin
McConlogue, Lisa
Buttini, Manuel
Games, Dora
Schenk, Dale
author_facet Masliah, Eliezer
Rockenstein, Edward
Mante, Michael
Crews, Leslie
Spencer, Brian
Adame, Anthony
Patrick, Christina
Trejo, Margarita
Ubhi, Kiren
Rohn, Troy T.
Mueller-Steiner, Sarah
Seubert, Peter
Barbour, Robin
McConlogue, Lisa
Buttini, Manuel
Games, Dora
Schenk, Dale
author_sort Masliah, Eliezer
collection PubMed
description Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB.
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spelling pubmed-30848382011-05-10 Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease Masliah, Eliezer Rockenstein, Edward Mante, Michael Crews, Leslie Spencer, Brian Adame, Anthony Patrick, Christina Trejo, Margarita Ubhi, Kiren Rohn, Troy T. Mueller-Steiner, Sarah Seubert, Peter Barbour, Robin McConlogue, Lisa Buttini, Manuel Games, Dora Schenk, Dale PLoS One Research Article Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB. Public Library of Science 2011-04-29 /pmc/articles/PMC3084838/ /pubmed/21559417 http://dx.doi.org/10.1371/journal.pone.0019338 Text en Masliah et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Masliah, Eliezer
Rockenstein, Edward
Mante, Michael
Crews, Leslie
Spencer, Brian
Adame, Anthony
Patrick, Christina
Trejo, Margarita
Ubhi, Kiren
Rohn, Troy T.
Mueller-Steiner, Sarah
Seubert, Peter
Barbour, Robin
McConlogue, Lisa
Buttini, Manuel
Games, Dora
Schenk, Dale
Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
title Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
title_full Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
title_fullStr Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
title_full_unstemmed Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
title_short Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
title_sort passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of lewy body disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084838/
https://www.ncbi.nlm.nih.gov/pubmed/21559417
http://dx.doi.org/10.1371/journal.pone.0019338
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