ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it>
<p>Abstract</p> <p>Background</p> <p>Apolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ clearance. We previously showed that an apoE-derived peptide...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-04-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/5/1/16 |
| _version_ | 1818668299977752576 |
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| author | Pak Daniel TS Turner R Scott Dakshanamurthy Sivanesan Davis Gary C Babus Lenard W Tesoriero Joseph A Cirrito John R Cordova Antoinette Minami S Sakura Rebeck G William Paige Mikell Hoe Hyang-Sook |
| author_facet | Pak Daniel TS Turner R Scott Dakshanamurthy Sivanesan Davis Gary C Babus Lenard W Tesoriero Joseph A Cirrito John R Cordova Antoinette Minami S Sakura Rebeck G William Paige Mikell Hoe Hyang-Sook |
| author_sort | Pak Daniel TS |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Apolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ clearance. We previously showed that an apoE-derived peptide containing a double repeat of the receptor-binding region was similarly effective in increasing APP processing <it>in vivo</it>. Here, we further examined whether peptides containing tandem repeats of the apoE receptor-binding region (amino acids 141-149) affected APP trafficking, APP processing, and Aβ production.</p> <p>Results</p> <p>We found that peptides containing a double or triple tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased cell surface APP and decreased Aβ levels in PS1-overexpressing PS70 cells and in primary neurons. This effect was potentiated by a sequential increase in the number of apoE receptor-binding domain repeats (trimer > dimer > monomer). We previously showed that the apoE dimer increased APP CTF <it>in vivo</it>; to determine whether the dimer also affected secreted APP or Aβ levels, we performed a single hippocampal injection of the apoE dimer in wild-type mice and analyzed its effect on APP processing. We found increased sAPPα and decreased Aβ levels at 24 hrs after treatment, suggesting that the apoE dimer may increase α-secretase cleavage.</p> <p>Conclusions</p> <p>These data suggest that small peptides consisting of tandem repeats of the apoE receptor-binding region are sufficient to alter APP trafficking and processing. The potency of these peptides increased with increasing repeats of the receptor binding domain of apoE. In addition, <it>in vivo </it>administration of the apoE peptide (dimer) increased sAPPα and decreased Aβ levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Aβ production both <it>in vitro </it>and <it>in vivo</it>.</p> |
| first_indexed | 2024-12-17T06:34:07Z |
| format | Article |
| id | doaj.art-cf1af75a2761479db585c61d05b36fd3 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-17T06:34:07Z |
| publishDate | 2010-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-cf1af75a2761479db585c61d05b36fd32022-12-21T22:00:04ZengBMCMolecular Neurodegeneration1750-13262010-04-01511610.1186/1750-1326-5-16ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it>Pak Daniel TSTurner R ScottDakshanamurthy SivanesanDavis Gary CBabus Lenard WTesoriero Joseph ACirrito John RCordova AntoinetteMinami S SakuraRebeck G WilliamPaige MikellHoe Hyang-Sook<p>Abstract</p> <p>Background</p> <p>Apolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ clearance. We previously showed that an apoE-derived peptide containing a double repeat of the receptor-binding region was similarly effective in increasing APP processing <it>in vivo</it>. Here, we further examined whether peptides containing tandem repeats of the apoE receptor-binding region (amino acids 141-149) affected APP trafficking, APP processing, and Aβ production.</p> <p>Results</p> <p>We found that peptides containing a double or triple tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased cell surface APP and decreased Aβ levels in PS1-overexpressing PS70 cells and in primary neurons. This effect was potentiated by a sequential increase in the number of apoE receptor-binding domain repeats (trimer > dimer > monomer). We previously showed that the apoE dimer increased APP CTF <it>in vivo</it>; to determine whether the dimer also affected secreted APP or Aβ levels, we performed a single hippocampal injection of the apoE dimer in wild-type mice and analyzed its effect on APP processing. We found increased sAPPα and decreased Aβ levels at 24 hrs after treatment, suggesting that the apoE dimer may increase α-secretase cleavage.</p> <p>Conclusions</p> <p>These data suggest that small peptides consisting of tandem repeats of the apoE receptor-binding region are sufficient to alter APP trafficking and processing. The potency of these peptides increased with increasing repeats of the receptor binding domain of apoE. In addition, <it>in vivo </it>administration of the apoE peptide (dimer) increased sAPPα and decreased Aβ levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Aβ production both <it>in vitro </it>and <it>in vivo</it>.</p>http://www.molecularneurodegeneration.com/content/5/1/16 |
| spellingShingle | Pak Daniel TS Turner R Scott Dakshanamurthy Sivanesan Davis Gary C Babus Lenard W Tesoriero Joseph A Cirrito John R Cordova Antoinette Minami S Sakura Rebeck G William Paige Mikell Hoe Hyang-Sook ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it> Molecular Neurodegeneration |
| title | ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it> |
| title_full | ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it> |
| title_fullStr | ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it> |
| title_full_unstemmed | ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it> |
| title_short | ApoE mimetic peptide decreases Aβ production <it>in vitro </it>and <it>in vivo</it> |
| title_sort | apoe mimetic peptide decreases aβ production it in vitro it and it in vivo it |
| url | http://www.molecularneurodegeneration.com/content/5/1/16 |
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