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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3031588?pdf=render |
| _version_ | 1818984452612685824 |
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| author | Brian Spencer Robert A Marr Ryan Gindi Rewati Potkar Sarah Michael Anthony Adame Edward Rockenstein Inder M Verma Eliezer Masliah |
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T18:19:14Z |
| format | Article |
| id | doaj.art-f14e2b21522a4a819eefd31029fe5038 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T18:19:14Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f14e2b21522a4a819eefd31029fe50382022-12-21T19:30:18ZengPublic 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 |
| 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 |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC3031588?pdf=render |
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