Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we util...

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Main Authors: Brian Spencer, Robert A Marr, Ryan Gindi, Rewati Potkar, Sarah Michael, Anthony Adame, Edward Rockenstein, Inder M Verma, Eliezer Masliah
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3031588?pdf=render
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spelling doaj-f14e2b21522a4a819eefd31029fe50382020-11-25T02:06:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1657510.1371/journal.pone.0016575Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.Brian SpencerRobert A MarrRyan GindiRewati PotkarSarah MichaelAnthony AdameEdward RockensteinInder M VermaEliezer MasliahAlzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.http://europepmc.org/articles/PMC3031588?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Brian Spencer
Robert A Marr
Ryan Gindi
Rewati Potkar
Sarah Michael
Anthony Adame
Edward Rockenstein
Inder M Verma
Eliezer Masliah
spellingShingle Brian Spencer
Robert A Marr
Ryan Gindi
Rewati Potkar
Sarah Michael
Anthony Adame
Edward Rockenstein
Inder M Verma
Eliezer Masliah
Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.
PLoS ONE
author_facet Brian Spencer
Robert A Marr
Ryan Gindi
Rewati Potkar
Sarah Michael
Anthony Adame
Edward Rockenstein
Inder M Verma
Eliezer Masliah
author_sort Brian Spencer
title Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.
title_short Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.
title_full Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.
title_fullStr Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.
title_full_unstemmed Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.
title_sort peripheral delivery of a cns targeted, metalo-protease reduces aβ toxicity in a mouse model of alzheimer's disease.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.
url http://europepmc.org/articles/PMC3031588?pdf=render
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