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

Eliezer Masliah; Edward Rockenstein; Michael Mante; Leslie Crews; Brian Spencer; Anthony Adame; Christina Patrick; Margarita Trejo; Kiren Ubhi; Troy T. Rohn; Sarah Mueller-Steiner; Peter Seubert; Robin Barbour; Lisa McConlogue; Manuel Buttini; Dora Games; Dale Schenk

doi:10.1371/journal.pone.0019338

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

Eliezer Masliah, Edward Rockenstein, Michael Mante, Leslie Crews, Brian Spencer, Anthony Adame, Christina Patrick, Margarita Trejo, Kiren Ubhi, Troy T. Rohn, Sarah Mueller-Steiner, Peter Seubert, Robin Barbour, Lisa McConlogue, Manuel Buttini, Dora Games, Dale Schenk

Biological Sciences

Research output: Contribution to journal › Article › peer-review

393 Scopus citations

Abstract

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.

Original language	American English
Article number	e19338
Journal	History Faculty Publications and Presentations
Volume	6
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0019338
State	Published - 29 Apr 2011

Keywords

Immunization, Passive/methods
Antibodies, Monoclonal/metabolism
Rats
Lysosomes/metabolism
Mice, Transgenic
Behavior, Animal
Immunohistochemistry/methods
Animals
Maze Learning
alpha-Synuclein/genetics
Cell Line, Tumor
Lewy Body Disease/genetics
Nerve Degeneration/pathology
Mice
Disease Models, Animal

EGS Disciplines

Biology

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https://scholarworks.boisestate.edu/bio_facpubs/72License: CC BY-NC-SA

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Masliah, E., Rockenstein, E., Mante, M., Crews, L., Spencer, B., Adame, A., Patrick, C., Trejo, M., Ubhi, K., Rohn, T. T., Mueller-Steiner, S., Seubert, P., Barbour, R., McConlogue, L., Buttini, M., Games, D., & Schenk, D. (2011). Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease. History Faculty Publications and Presentations, 6(4), Article e19338. https://doi.org/10.1371/journal.pone.0019338

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

abstract = " 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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author = "Eliezer Masliah and Edward Rockenstein and Michael Mante and Leslie Crews and Brian Spencer and Anthony Adame and Christina Patrick and Margarita Trejo and Kiren Ubhi and Rohn, \{Troy T.\} and Sarah Mueller-Steiner and Peter Seubert and Robin Barbour and Lisa McConlogue and Manuel Buttini and Dora Games and Dale Schenk",

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Masliah, E, Rockenstein, E, Mante, M, Crews, L, Spencer, B, Adame, A, Patrick, C, Trejo, M, Ubhi, K, Rohn, TT, Mueller-Steiner, S, Seubert, P, Barbour, R, McConlogue, L, Buttini, M, Games, D & Schenk, D 2011, 'Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease', History Faculty Publications and Presentations, vol. 6, no. 4, e19338. https://doi.org/10.1371/journal.pone.0019338

TY - JOUR

T1 - Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

AU - Masliah, Eliezer

AU - Rockenstein, Edward

AU - Mante, Michael

AU - Crews, Leslie

AU - Spencer, Brian

AU - Adame, Anthony

AU - Patrick, Christina

AU - Trejo, Margarita

AU - Ubhi, Kiren

AU - Rohn, Troy T.

AU - Mueller-Steiner, Sarah

AU - Seubert, Peter

AU - Barbour, Robin

AU - McConlogue, Lisa

AU - Buttini, Manuel

AU - Games, Dora

AU - Schenk, Dale

PY - 2011/4/29

Y1 - 2011/4/29

N2 - 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.

AB - 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.

KW - Immunization, Passive/methods

KW - Antibodies, Monoclonal/metabolism

KW - Rats

KW - Lysosomes/metabolism

KW - Mice, Transgenic

KW - Behavior, Animal

KW - Immunohistochemistry/methods

KW - Animals

KW - Maze Learning

KW - alpha-Synuclein/genetics

KW - Cell Line, Tumor

KW - Lewy Body Disease/genetics

KW - Nerve Degeneration/pathology

KW - Mice

KW - Disease Models, Animal

UR - https://www.scopus.com/pages/publications/79955757052

U2 - 10.1371/journal.pone.0019338

DO - 10.1371/journal.pone.0019338

M3 - Article

C2 - 21559417

VL - 6

JO - History Faculty Publications and Presentations

JF - History Faculty Publications and Presentations

IS - 4

M1 - e19338

ER -

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

Abstract

Keywords

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