TY - JOUR
T1 - Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease
AU - Rohn, Troy
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 - 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.
UR - https://scholarworks.boisestate.edu/bio_facpubs/72
UR - http://www.scopus.com/inward/record.url?scp=79955757052&partnerID=8YFLogxK
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 -