A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers.
Identifieur interne : 000159 ( Main/Exploration ); précédent : 000158; suivant : 000160A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers.
Auteurs : Tetsushi Kataura [Japon] ; Etsu Tashiro [Japon] ; Shota Nishikawa [Japon] ; Kensuke Shibahara [Japon] ; Yoshihito Muraoka [Japon] ; Masahiro Miura [Japon] ; Shun Sakai [Japon] ; Naohiro Katoh [Japon] ; Misato Totsuka [Japon] ; Masafumi Onodera [Japon] ; Kazuo Shin-Ya [Japon] ; Kengo Miyamoto [Japon] ; Yukiko Sasazawa [Japon] ; Nobutaka Hattori [Japon] ; Shinji Saiki [Japon] ; Masaya Imoto [Japon]Source :
- Autophagy [ 1554-8635 ] ; 2020.
Abstract
Macroautophagy/autophagy plays a critical role in the pathogenesis of various human diseases including neurodegenerative disorders such as Parkinson disease (PD) and Huntington disease (HD). Chemical autophagy inducers are expected to serve as disease-modifying agents by eliminating cytotoxic/damaged proteins. Although many autophagy inducers have been identified, their precise molecular mechanisms are not fully understood because of the complicated crosstalk among signaling pathways. To address this issue, we performed several chemical genomic analyses enabling us to comprehend the dominancy among the autophagy-associated pathways followed by an aggresome-clearance assay. In a first step, more than 400 target-established small molecules were assessed for their ability to activate autophagic flux in neuronal PC12D cells, and we identified 39 compounds as autophagy inducers. We then profiled the autophagy inducers by testing their effect on the induction of autophagy by 200 well-established signal transduction modulators. Our principal component analysis (PCA) and clustering analysis using a dataset of "autophagy profiles" revealed that two Food and Drug Administration (FDA)-approved drugs, memantine and clemastine, activate endoplasmic reticulum (ER) stress responses, which could lead to autophagy induction. We also confirmed that SMK-17, a recently identified autophagy inducer, induced autophagy via the PRKC/PKC-TFEB pathway, as had been predicted from PCA. Finally, we showed that almost all of the autophagy inducers tested in this present work significantly enhanced the clearance of the protein aggregates observed in cellular models of PD and HD. These results, with the combined approach, suggested that autophagy-activating small molecules may improve proteinopathies by eliminating nonfunctional protein aggregates.
ABBREVIATIONS
ADK: adenosine kinase; AMPK: AMP-activated protein kinase; ATF4: activating transcription factor 4; BECN1: beclin-1; DDIT3/CHOP: DNA damage inducible transcript 3; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 subunit alpha; ER: endoplasmic reticulum; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FDA: Food and Drug Administration; GSH: glutathione; HD: Huntington disease; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; HTT: huntingtin; JAK: Janus kinase, MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MAP2K/MEK: mitogen-activated protein kinase kinase; MAP3K8/Tpl2: mitogen-activated protein kinase kinase kinase 8; MAPK: mitogen-activated protein kinase; MPP
DOI: 10.1080/15548627.2020.1794590
PubMed: 32762399
Affiliations:
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xml:lang="fr">Japon</country><wicri:regionArea>National Institute of Advanced Industrial Science and Technology , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Biotechnology Research Centre, The University of Tokyo , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Biotechnology Research Centre, The University of Tokyo , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , 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Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Juntendo University School of Medicine , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of 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Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32762399</idno><idno type="pmid">32762399</idno><idno type="doi">10.1080/15548627.2020.1794590</idno><idno type="wicri:Area/Main/Corpus">000034</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000034</idno><idno type="wicri:Area/Main/Curation">000034</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000034</idno><idno type="wicri:Area/Main/Exploration">000034</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers.</title><author><name sortKey="Kataura, Tetsushi" sort="Kataura, Tetsushi" uniqKey="Kataura T" first="Tetsushi" last="Kataura">Tetsushi Kataura</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:affiliation>Research Fellow of the Japan Society for the Promotion of Science (JSPS) , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Research Fellow of the Japan Society for the Promotion of Science (JSPS) , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Tashiro, Etsu" sort="Tashiro, Etsu" uniqKey="Tashiro E" first="Etsu" last="Tashiro">Etsu Tashiro</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Nishikawa, Shota" sort="Nishikawa, Shota" uniqKey="Nishikawa S" first="Shota" last="Nishikawa">Shota Nishikawa</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Shibahara, Kensuke" sort="Shibahara, Kensuke" uniqKey="Shibahara K" first="Kensuke" last="Shibahara">Kensuke Shibahara</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Muraoka, Yoshihito" sort="Muraoka, Yoshihito" uniqKey="Muraoka Y" first="Yoshihito" last="Muraoka">Yoshihito Muraoka</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Miura, Masahiro" sort="Miura, Masahiro" uniqKey="Miura M" first="Masahiro" last="Miura">Masahiro Miura</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Sakai, Shun" sort="Sakai, Shun" uniqKey="Sakai S" first="Shun" last="Sakai">Shun Sakai</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Katoh, Naohiro" sort="Katoh, Naohiro" uniqKey="Katoh N" first="Naohiro" last="Katoh">Naohiro Katoh</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Totsuka, Misato" sort="Totsuka, Misato" uniqKey="Totsuka M" first="Misato" last="Totsuka">Misato Totsuka</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author><author><name sortKey="Onodera, Masafumi" sort="Onodera, Masafumi" uniqKey="Onodera M" first="Masafumi" last="Onodera">Masafumi Onodera</name><affiliation wicri:level="3"><nlm:affiliation>Division of Immunology, National Center for Child Health and Development , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Immunology, National Center for Child Health and Development , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Shin Ya, Kazuo" sort="Shin Ya, Kazuo" uniqKey="Shin Ya K" first="Kazuo" last="Shin-Ya">Kazuo Shin-Ya</name><affiliation wicri:level="3"><nlm:affiliation>National Institute of Advanced Industrial Science and Technology , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>National Institute of Advanced Industrial Science and Technology , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Biotechnology Research Centre, The University of Tokyo , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Biotechnology Research Centre, The University of Tokyo , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Miyamoto, Kengo" sort="Miyamoto, Kengo" uniqKey="Miyamoto K" first="Kengo" last="Miyamoto">Kengo Miyamoto</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Juntendo University School of Medicine , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Sasazawa, Yukiko" sort="Sasazawa, Yukiko" uniqKey="Sasazawa Y" first="Yukiko" last="Sasazawa">Yukiko Sasazawa</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Juntendo University School of Medicine , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Juntendo University School of Medicine , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Saiki, Shinji" sort="Saiki, Shinji" uniqKey="Saiki S" first="Shinji" last="Saiki">Shinji Saiki</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Juntendo University School of Medicine , Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Imoto, Masaya" sort="Imoto, Masaya" uniqKey="Imoto M" first="Masaya" last="Imoto">Masaya Imoto</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biosciences and Informatics, Keio University , Kanagawa</wicri:regionArea><wicri:noRegion>Kanagawa</wicri:noRegion></affiliation></author></analytic><series><title level="j">Autophagy</title><idno type="eISSN">1554-8635</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Macroautophagy/autophagy plays a critical role in the pathogenesis of various human diseases including neurodegenerative disorders such as Parkinson disease (PD) and Huntington disease (HD). Chemical autophagy inducers are expected to serve as disease-modifying agents by eliminating cytotoxic/damaged proteins. Although many autophagy inducers have been identified, their precise molecular mechanisms are not fully understood because of the complicated crosstalk among signaling pathways. To address this issue, we performed several chemical genomic analyses enabling us to comprehend the dominancy among the autophagy-associated pathways followed by an aggresome-clearance assay. In a first step, more than 400 target-established small molecules were assessed for their ability to activate autophagic flux in neuronal PC12D cells, and we identified 39 compounds as autophagy inducers. We then profiled the autophagy inducers by testing their effect on the induction of autophagy by 200 well-established signal transduction modulators. Our principal component analysis (PCA) and clustering analysis using a dataset of "autophagy profiles" revealed that two Food and Drug Administration (FDA)-approved drugs, memantine and clemastine, activate endoplasmic reticulum (ER) stress responses, which could lead to autophagy induction. We also confirmed that SMK-17, a recently identified autophagy inducer, induced autophagy via the PRKC/PKC-TFEB pathway, as had been predicted from PCA. Finally, we showed that almost all of the autophagy inducers tested in this present work significantly enhanced the clearance of the protein aggregates observed in cellular models of PD and HD. These results, with the combined approach, suggested that autophagy-activating small molecules may improve proteinopathies by eliminating nonfunctional protein aggregates.</div><div type="abstract" xml:lang="en"><p><b>ABBREVIATIONS</b></p><p>ADK: adenosine kinase; AMPK: AMP-activated protein kinase; ATF4: activating transcription factor 4; BECN1: beclin-1; DDIT3/CHOP: DNA damage inducible transcript 3; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 subunit alpha; ER: endoplasmic reticulum; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FDA: Food and Drug Administration; GSH: glutathione; HD: Huntington disease; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; HTT: huntingtin; JAK: Janus kinase, MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MAP2K/MEK: mitogen-activated protein kinase kinase; MAP3K8/Tpl2: mitogen-activated protein kinase kinase kinase 8; MAPK: mitogen-activated protein kinase; MPP</p></div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32762399</PMID><DateRevised><Year>2020</Year><Month>08</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1554-8635</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Aug</Month><Day>07</Day></PubDate></JournalIssue><Title>Autophagy</Title><ISOAbbreviation>Autophagy</ISOAbbreviation></Journal><ArticleTitle>A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers.</ArticleTitle><Pagination><MedlinePgn>1-17</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/15548627.2020.1794590</ELocationID><Abstract><AbstractText>Macroautophagy/autophagy plays a critical role in the pathogenesis of various human diseases including neurodegenerative disorders such as Parkinson disease (PD) and Huntington disease (HD). Chemical autophagy inducers are expected to serve as disease-modifying agents by eliminating cytotoxic/damaged proteins. Although many autophagy inducers have been identified, their precise molecular mechanisms are not fully understood because of the complicated crosstalk among signaling pathways. To address this issue, we performed several chemical genomic analyses enabling us to comprehend the dominancy among the autophagy-associated pathways followed by an aggresome-clearance assay. In a first step, more than 400 target-established small molecules were assessed for their ability to activate autophagic flux in neuronal PC12D cells, and we identified 39 compounds as autophagy inducers. We then profiled the autophagy inducers by testing their effect on the induction of autophagy by 200 well-established signal transduction modulators. Our principal component analysis (PCA) and clustering analysis using a dataset of "autophagy profiles" revealed that two Food and Drug Administration (FDA)-approved drugs, memantine and clemastine, activate endoplasmic reticulum (ER) stress responses, which could lead to autophagy induction. We also confirmed that SMK-17, a recently identified autophagy inducer, induced autophagy via the PRKC/PKC-TFEB pathway, as had been predicted from PCA. Finally, we showed that almost all of the autophagy inducers tested in this present work significantly enhanced the clearance of the protein aggregates observed in cellular models of PD and HD. These results, with the combined approach, suggested that autophagy-activating small molecules may improve proteinopathies by eliminating nonfunctional protein aggregates.</AbstractText><AbstractText Label="ABBREVIATIONS" NlmCategory="BACKGROUND">ADK: adenosine kinase; AMPK: AMP-activated protein kinase; ATF4: activating transcription factor 4; BECN1: beclin-1; DDIT3/CHOP: DNA damage inducible transcript 3; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 subunit alpha; ER: endoplasmic reticulum; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FDA: Food and Drug Administration; GSH: glutathione; HD: Huntington disease; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; HTT: huntingtin; JAK: Janus kinase, MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MAP2K/MEK: mitogen-activated protein kinase kinase; MAP3K8/Tpl2: mitogen-activated protein kinase kinase kinase 8; MAPK: mitogen-activated protein kinase; MPP<sup>+</sup>: 1-methyl-4-phenylpyridinium; MTOR: mechanistic target of rapamycin kinase; MTORC: MTOR complex; NAC: N-acetylcysteine; NGF: nerve growth factor 2; NMDA: N-methyl-D-aspartate; PCA: principal component analysis; PD: Parkinson disease; PDA: pancreatic ductal adenocarcinoma; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PMA: phorbol 12-myristate 13-acetate; PRKC/PKC: protein kinase C; ROCK: Rho-associated coiled-coil protein kinase; RR: ribonucleotide reductase; SIGMAR1: sigma non-opioid intracellular receptor 1; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TFEB: Transcription factor EB; TGFB/TGF-β: Transforming growth factor beta; ULK1: unc-51 like autophagy activating kinase 1; XBP1: X-box binding protein 1.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kataura</LastName><ForeName>Tetsushi</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Fellow of the Japan Society for the Promotion of Science (JSPS) , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tashiro</LastName><ForeName>Etsu</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nishikawa</LastName><ForeName>Shota</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shibahara</LastName><ForeName>Kensuke</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Muraoka</LastName><ForeName>Yoshihito</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miura</LastName><ForeName>Masahiro</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sakai</LastName><ForeName>Shun</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Katoh</LastName><ForeName>Naohiro</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Totsuka</LastName><ForeName>Misato</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Onodera</LastName><ForeName>Masafumi</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Immunology, National Center for Child Health and Development , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin-Ya</LastName><ForeName>Kazuo</ForeName><Initials>K</Initials><Identifier Source="ORCID">https://orcid.org/0000-0002-4702-0661</Identifier><AffiliationInfo><Affiliation>National Institute of Advanced Industrial Science and Technology , Tokyo, Japan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biotechnology Research Centre, The University of Tokyo , Tokyo, Japan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miyamoto</LastName><ForeName>Kengo</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sasazawa</LastName><ForeName>Yukiko</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hattori</LastName><ForeName>Nobutaka</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saiki</LastName><ForeName>Shinji</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Neurology, Juntendo University School of Medicine , Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Imoto</LastName><ForeName>Masaya</ForeName><Initials>M</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-4910-3871</Identifier><AffiliationInfo><Affiliation>Department of Biosciences and Informatics, Keio University , Kanagawa, Japan.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>08</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Autophagy</MedlineTA><NlmUniqueID>101265188</NlmUniqueID><ISSNLinking>1554-8627</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Aggrephagy</Keyword><Keyword MajorTopicYN="N">PRKC/PKC</Keyword><Keyword MajorTopicYN="N">TFEB</Keyword><Keyword MajorTopicYN="N">chemical genomics</Keyword><Keyword MajorTopicYN="N">neurodegenerative disease</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32762399</ArticleId><ArticleId IdType="doi">10.1080/15548627.2020.1794590</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><noRegion><name sortKey="Kataura, Tetsushi" sort="Kataura, Tetsushi" uniqKey="Kataura T" first="Tetsushi" last="Kataura">Tetsushi Kataura</name></noRegion><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><name sortKey="Imoto, Masaya" sort="Imoto, Masaya" uniqKey="Imoto M" first="Masaya" last="Imoto">Masaya Imoto</name><name sortKey="Kataura, Tetsushi" sort="Kataura, Tetsushi" uniqKey="Kataura T" first="Tetsushi" last="Kataura">Tetsushi Kataura</name><name sortKey="Katoh, Naohiro" sort="Katoh, Naohiro" uniqKey="Katoh N" first="Naohiro" last="Katoh">Naohiro Katoh</name><name sortKey="Miura, Masahiro" sort="Miura, Masahiro" uniqKey="Miura M" first="Masahiro" last="Miura">Masahiro Miura</name><name sortKey="Miyamoto, Kengo" sort="Miyamoto, Kengo" uniqKey="Miyamoto K" first="Kengo" last="Miyamoto">Kengo Miyamoto</name><name sortKey="Muraoka, Yoshihito" sort="Muraoka, Yoshihito" uniqKey="Muraoka Y" first="Yoshihito" last="Muraoka">Yoshihito Muraoka</name><name sortKey="Nishikawa, Shota" sort="Nishikawa, Shota" uniqKey="Nishikawa S" first="Shota" last="Nishikawa">Shota Nishikawa</name><name sortKey="Onodera, Masafumi" sort="Onodera, Masafumi" uniqKey="Onodera M" first="Masafumi" last="Onodera">Masafumi Onodera</name><name sortKey="Saiki, Shinji" sort="Saiki, Shinji" uniqKey="Saiki S" first="Shinji" last="Saiki">Shinji Saiki</name><name sortKey="Sakai, Shun" sort="Sakai, Shun" uniqKey="Sakai S" first="Shun" last="Sakai">Shun Sakai</name><name sortKey="Sasazawa, Yukiko" sort="Sasazawa, Yukiko" uniqKey="Sasazawa Y" first="Yukiko" last="Sasazawa">Yukiko Sasazawa</name><name sortKey="Sasazawa, Yukiko" sort="Sasazawa, Yukiko" uniqKey="Sasazawa Y" first="Yukiko" last="Sasazawa">Yukiko Sasazawa</name><name sortKey="Shibahara, Kensuke" sort="Shibahara, Kensuke" uniqKey="Shibahara K" first="Kensuke" last="Shibahara">Kensuke Shibahara</name><name sortKey="Shin Ya, Kazuo" sort="Shin Ya, Kazuo" uniqKey="Shin Ya K" first="Kazuo" last="Shin-Ya">Kazuo Shin-Ya</name><name sortKey="Shin Ya, Kazuo" sort="Shin Ya, Kazuo" uniqKey="Shin Ya K" first="Kazuo" last="Shin-Ya">Kazuo Shin-Ya</name><name sortKey="Shin Ya, Kazuo" sort="Shin Ya, Kazuo" uniqKey="Shin Ya K" first="Kazuo" last="Shin-Ya">Kazuo Shin-Ya</name><name sortKey="Tashiro, Etsu" sort="Tashiro, Etsu" uniqKey="Tashiro E" first="Etsu" last="Tashiro">Etsu Tashiro</name><name sortKey="Totsuka, Misato" sort="Totsuka, Misato" uniqKey="Totsuka M" first="Misato" last="Totsuka">Misato Totsuka</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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