BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice
ABSTRACT: β-amyloid (Aβ) is produced by the β-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer’s disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown...
- Autores:
-
Barrera Ocampo, Álvaro Andrés
Piedrahita, Diego
Velásquez Rodríguez, Claudia María
Arias Londoño, Julián David
Cardona Gómez, Gloria Patricia
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2016
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/8398
- Acceso en línea:
- http://hdl.handle.net/10495/8398
- Palabra clave:
- Enfermedad de Alzheimer
Cognitivismo
Fosfolípidos
Funciones cognitivas
Interferencia de ARN
- Rights
- openAccess
- License
- Atribución 2.5 Colombia (CC BY 2.5 CO)
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| dc.title.spa.fl_str_mv |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| title |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| spellingShingle |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice Enfermedad de Alzheimer Cognitivismo Fosfolípidos Funciones cognitivas Interferencia de ARN |
| title_short |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| title_full |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| title_fullStr |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| title_full_unstemmed |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| title_sort |
BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice |
| dc.creator.fl_str_mv |
Barrera Ocampo, Álvaro Andrés Piedrahita, Diego Velásquez Rodríguez, Claudia María Arias Londoño, Julián David Cardona Gómez, Gloria Patricia |
| dc.contributor.author.none.fl_str_mv |
Barrera Ocampo, Álvaro Andrés Piedrahita, Diego Velásquez Rodríguez, Claudia María Arias Londoño, Julián David Cardona Gómez, Gloria Patricia |
| dc.subject.none.fl_str_mv |
Enfermedad de Alzheimer Cognitivismo Fosfolípidos Funciones cognitivas Interferencia de ARN |
| topic |
Enfermedad de Alzheimer Cognitivismo Fosfolípidos Funciones cognitivas Interferencia de ARN |
| description |
ABSTRACT: β-amyloid (Aβ) is produced by the β-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer’s disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism. The objective of this study was to determine the effect of RNA interference against BACE1 (shBACEmiR) on the phospholipid profile in hippocampal CA1 area in aged 3xTg-AD mice after 6 and 12 months of treatment compared to aged PS1KI mice. The shBACEmiR treatment induced cognitive function recovery and restored mainly the fatty acid composition of lysophosphatidylethanolamine and etherphosphatidylethanolamine, reduced the cPLA2’s phosphorylation, down-regulated the levels of arachidonic acid and COX2 in the hippocampi of 3xTg-AD mice. Together, our findings suggest, for the first time, that BACE1 silencing restores phospholipids composition which could favor the recovery of cellular homeostasis and cognitive function in the hippocampus of triple transgenic AD mice. Keywords: Alzheimer’s disease, phospholipids, BACE1, RNA interference, hippocampus, cognitive function |
| publishDate |
2016 |
| dc.date.issued.none.fl_str_mv |
2016 |
| dc.date.accessioned.none.fl_str_mv |
2017-09-28T18:45:32Z |
| dc.date.available.none.fl_str_mv |
2017-09-28T18:45:32Z |
| dc.type.spa.fl_str_mv |
info:eu-repo/semantics/article |
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http://purl.org/coar/version/c_970fb48d4fbd8a86 http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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https://purl.org/redcol/resource_type/ART |
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Artículo de investigación |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.identifier.citation.spa.fl_str_mv |
Villamil-Ortiz J, Barrera-Ocampo A, Piedrahita D, Velásquez-Rodríguez C, Arias-Londoño J, Cardona-Gómez G. BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice. Frontiers in Cellular Neuroscience. 2016; 10(260): 1-14. |
| dc.identifier.issn.none.fl_str_mv |
1662-5102 |
| dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10495/8398 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fncel.2016.00260 |
| identifier_str_mv |
Villamil-Ortiz J, Barrera-Ocampo A, Piedrahita D, Velásquez-Rodríguez C, Arias-Londoño J, Cardona-Gómez G. BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice. Frontiers in Cellular Neuroscience. 2016; 10(260): 1-14. 1662-5102 10.3389/fncel.2016.00260 |
| url |
http://hdl.handle.net/10495/8398 |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Front Cell Neurosci |
| dc.rights.*.fl_str_mv |
Atribución 2.5 Colombia (CC BY 2.5 CO) |
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info:eu-repo/semantics/openAccess |
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https://creativecommons.org/licenses/by/2.5/co/ |
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Atribución 2.5 Colombia (CC BY 2.5 CO) https://creativecommons.org/licenses/by/2.5/co/ http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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13 |
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application/pdf |
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Frontiers Research Foundation |
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Grupo de Neurociencias de Antioquia |
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Suiza |
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Universidad de Antioquia |
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Barrera Ocampo, Álvaro AndrésPiedrahita, DiegoVelásquez Rodríguez, Claudia MaríaArias Londoño, Julián DavidCardona Gómez, Gloria Patricia2017-09-28T18:45:32Z2017-09-28T18:45:32Z2016Villamil-Ortiz J, Barrera-Ocampo A, Piedrahita D, Velásquez-Rodríguez C, Arias-Londoño J, Cardona-Gómez G. BACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD mice. Frontiers in Cellular Neuroscience. 2016; 10(260): 1-14.1662-5102http://hdl.handle.net/10495/839810.3389/fncel.2016.00260ABSTRACT: β-amyloid (Aβ) is produced by the β-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer’s disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism. The objective of this study was to determine the effect of RNA interference against BACE1 (shBACEmiR) on the phospholipid profile in hippocampal CA1 area in aged 3xTg-AD mice after 6 and 12 months of treatment compared to aged PS1KI mice. The shBACEmiR treatment induced cognitive function recovery and restored mainly the fatty acid composition of lysophosphatidylethanolamine and etherphosphatidylethanolamine, reduced the cPLA2’s phosphorylation, down-regulated the levels of arachidonic acid and COX2 in the hippocampi of 3xTg-AD mice. Together, our findings suggest, for the first time, that BACE1 silencing restores phospholipids composition which could favor the recovery of cellular homeostasis and cognitive function in the hippocampus of triple transgenic AD mice. Keywords: Alzheimer’s disease, phospholipids, BACE1, RNA interference, hippocampus, cognitive function13application/pdfengFrontiers Research FoundationGrupo de Neurociencias de AntioquiaSuizainfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a86http://purl.org/coar/version/c_970fb48d4fbd8a85Atribución 2.5 Colombia (CC BY 2.5 CO)info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by/4.0/Enfermedad de AlzheimerCognitivismoFosfolípidosFunciones cognitivasInterferencia de ARNBACE1 RNAi restores the composition of phosphatidylethanolamine-derivates related to memory improvement in aged 3xTg-AD miceFront Cell NeurosciFrontiers in Cellular Neuroscience11410ORIGINALAriasJulian_2016_RestoresPhosphatidylethanolamine.pdfAriasJulian_2016_RestoresPhosphatidylethanolamine.pdfArtículo de investigaciónapplication/pdf2838383http://bibliotecadigital.udea.edu.co/bitstream/10495/8398/1/AriasJulian_2016_RestoresPhosphatidylethanolamine.pdfd731216c6b02a9fc9fba6d888c87ad50MD51CC-LICENSElicense_urllicense_urltext/plain; charset=utf-849http://bibliotecadigital.udea.edu.co/bitstream/10495/8398/2/license_url4afdbb8c545fd630ea7db775da747b2fMD52license_textlicense_texttext/html; charset=utf-80http://bibliotecadigital.udea.edu.co/bitstream/10495/8398/3/license_textd41d8cd98f00b204e9800998ecf8427eMD53license_rdflicense_rdfLicenciaapplication/rdf+xml; charset=utf-80http://bibliotecadigital.udea.edu.co/bitstream/10495/8398/4/license_rdfd41d8cd98f00b204e9800998ecf8427eMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/8398/5/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5510495/8398oai:bibliotecadigital.udea.edu.co:10495/83982021-06-19 11:42:23.597Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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 |