No significant effect of 7,8-dihydroxyflavone on APP processing and Alzheimer-associated phenotypes.
Identifieur interne : 000625 ( Main/Exploration ); précédent : 000624; suivant : 000626No significant effect of 7,8-dihydroxyflavone on APP processing and Alzheimer-associated phenotypes.
Auteurs : Weitao Zhou ; Xiaoyong Li ; Daochao Huang ; Weihui Zhou ; Tingyu Li ; Weihong Song [République populaire de Chine]Source :
- Current Alzheimer research [ 1875-5828 ] ; 2015.
English descriptors
- KwdEn :
- Alzheimer Disease (genetics), Amyloid beta-Peptides (metabolism), Amyloid beta-Protein Precursor (genetics), Amyloid beta-Protein Precursor (metabolism), Animals, Antipsychotic Agents (therapeutic use), Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Flavones (therapeutic use), HEK293 Cells, Humans, Maze Learning (drug effects), Mice, Mice, Transgenic, Mutation (genetics), Peptide Fragments (metabolism), Presenilin-1 (genetics), RNA, Messenger (metabolism), Time Factors, Transfection.
- MESH :
- chemical , genetics : Amyloid beta-Protein Precursor, Presenilin-1.
- chemical , metabolism : Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Peptide Fragments, RNA, Messenger.
- drug effects : Maze Learning.
- genetics : Alzheimer Disease, Mutation.
- chemical , therapeutic use : Antipsychotic Agents, Flavones.
- Animals, Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, Humans, Mice, Mice, Transgenic, Time Factors, Transfection.
Abstract
It is reported that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects on neuronal excitotoxicity, stroke, and Parkinson disease in animal models by enhancing axon regeneration, muscle reinnervation and neuromuscular transmission. The effect of DHF on AD neuropathology remains not well defined. In this study we examined whether DHF affects APP processing and cognitive functions in vitro and in vivo. We found that DHF had no significant effect on amyloid β precursor protein (APP), BACE1 and amyloid β protein (Aβ). DHF had little effect on APP processing in cell cultures. DHF treatment did not reduce the deposition of Aβ to form neuritic plaques in the brain of AD model mice APP23/PS45. Furthermore, DHF did not alleviate learning and memory impairments in the AD model mice. Our study suggest that further extensive and careful studies are warranted for considering DHF as a new therapeutic agent for reducing amyloid pathology and alleviating cognitive deficits for AD treatment.
PubMed: 25523427
Affiliations:
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Fax: 604-822-7756; or Children's Hospital of Chongqing Medical University, Chongqing 400014, China. weihong@mail.ubc.ca.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada; Fax: 604-822-7756; or Children's Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25523427</idno><idno type="pmid">25523427</idno><idno type="wicri:Area/PubMed/Corpus">000592</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000592</idno><idno type="wicri:Area/PubMed/Curation">000592</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000592</idno><idno type="wicri:Area/PubMed/Checkpoint">000592</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000592</idno><idno type="wicri:Area/Ncbi/Merge">001A07</idno><idno type="wicri:Area/Ncbi/Curation">001A07</idno><idno type="wicri:Area/Ncbi/Checkpoint">001A07</idno><idno type="wicri:Area/Main/Merge">000626</idno><idno type="wicri:Area/Main/Curation">000625</idno><idno type="wicri:Area/Main/Exploration">000625</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">No significant effect of 7,8-dihydroxyflavone on APP processing and Alzheimer-associated phenotypes.</title><author><name sortKey="Zhou, Weitao" sort="Zhou, Weitao" uniqKey="Zhou W" first="Weitao" last="Zhou">Weitao Zhou</name></author><author><name sortKey="Li, Xiaoyong" sort="Li, Xiaoyong" uniqKey="Li X" first="Xiaoyong" last="Li">Xiaoyong Li</name></author><author><name sortKey="Huang, Daochao" sort="Huang, Daochao" uniqKey="Huang D" first="Daochao" last="Huang">Daochao Huang</name></author><author><name sortKey="Zhou, Weihui" sort="Zhou, Weihui" uniqKey="Zhou W" first="Weihui" last="Zhou">Weihui Zhou</name></author><author><name sortKey="Li, Tingyu" sort="Li, Tingyu" uniqKey="Li T" first="Tingyu" last="Li">Tingyu Li</name></author><author><name sortKey="Song, Weihong" sort="Song, Weihong" uniqKey="Song W" first="Weihong" last="Song">Weihong Song</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada; Fax: 604-822-7756; or Children's Hospital of Chongqing Medical University, Chongqing 400014, China. weihong@mail.ubc.ca.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada; Fax: 604-822-7756; or Children's Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation></author></analytic><series><title level="j">Current Alzheimer research</title><idno type="eISSN">1875-5828</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alzheimer Disease (genetics)</term><term>Amyloid beta-Peptides (metabolism)</term><term>Amyloid beta-Protein Precursor (genetics)</term><term>Amyloid beta-Protein Precursor (metabolism)</term><term>Animals</term><term>Antipsychotic Agents (therapeutic use)</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flavones (therapeutic use)</term><term>HEK293 Cells</term><term>Humans</term><term>Maze Learning (drug effects)</term><term>Mice</term><term>Mice, Transgenic</term><term>Mutation (genetics)</term><term>Peptide Fragments (metabolism)</term><term>Presenilin-1 (genetics)</term><term>RNA, Messenger (metabolism)</term><term>Time Factors</term><term>Transfection</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Amyloid beta-Protein Precursor</term><term>Presenilin-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amyloid beta-Peptides</term><term>Amyloid beta-Protein Precursor</term><term>Peptide Fragments</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Maze Learning</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term><term>Mutation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antipsychotic Agents</term><term>Flavones</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Enzyme-Linked Immunosorbent Assay</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Time Factors</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">It is reported that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects on neuronal excitotoxicity, stroke, and Parkinson disease in animal models by enhancing axon regeneration, muscle reinnervation and neuromuscular transmission. The effect of DHF on AD neuropathology remains not well defined. In this study we examined whether DHF affects APP processing and cognitive functions in vitro and in vivo. We found that DHF had no significant effect on amyloid β precursor protein (APP), BACE1 and amyloid β protein (Aβ). DHF had little effect on APP processing in cell cultures. DHF treatment did not reduce the deposition of Aβ to form neuritic plaques in the brain of AD model mice APP23/PS45. Furthermore, DHF did not alleviate learning and memory impairments in the AD model mice. Our study suggest that further extensive and careful studies are warranted for considering DHF as a new therapeutic agent for reducing amyloid pathology and alleviating cognitive deficits for AD treatment.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Huang, Daochao" sort="Huang, Daochao" uniqKey="Huang D" first="Daochao" last="Huang">Daochao Huang</name><name sortKey="Li, Tingyu" sort="Li, Tingyu" uniqKey="Li T" first="Tingyu" last="Li">Tingyu Li</name><name sortKey="Li, Xiaoyong" sort="Li, Xiaoyong" uniqKey="Li X" first="Xiaoyong" last="Li">Xiaoyong Li</name><name sortKey="Zhou, Weihui" sort="Zhou, Weihui" uniqKey="Zhou W" first="Weihui" last="Zhou">Weihui Zhou</name><name sortKey="Zhou, Weitao" sort="Zhou, Weitao" uniqKey="Zhou W" first="Weitao" last="Zhou">Weitao Zhou</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Song, Weihong" sort="Song, Weihong" uniqKey="Song W" first="Weihong" last="Song">Weihong Song</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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