Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis
Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those proce...
Gespeichert in:
| Veröffentlicht in: | ACS chemical neuroscience 2019-05, Vol.10 (5), p.2584-2590 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2590 |
|---|---|
| container_issue | 5 |
| container_start_page | 2584 |
| container_title | ACS chemical neuroscience |
| container_volume | 10 |
| creator | Inoue, Masamichi Ueda, Mitsuharu Higashi, Taishi Anno, Takayuki Fujisawa, Kazuya Motoyama, Keiichi Mizuguchi, Mineyuki Ando, Yukio Jono, Hirofumi Arima, Hidetoshi |
| description | Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those processes are urgently needed. In this study, to discover a new drug candidate for ATTR amyloidosis therapy, we focused on polyamidoamine dendrimer (dendrimer), a 3D-structural nanomaterial, which has a branched cationic polymer repeating polyamidoamine units. Dendrimer (G2) not only inhibited ATTR V30M amyloid fibril formation, but also reduced already formed ATTR V30M amyloid fibrils by reducing β-sheet structure of ATTR V30M protein. Moreover, intravenous administration of dendrimer (G2) reduced TTR deposition in human ATTR V30M transgenic rats. These results indicate that dendrimer (G2) may possess both inhibitory and breaking effects on ATTR V30M amyloid, suggesting that dendrimer has the potential as a dual effective agents against TTR amyloidosis. |
| doi_str_mv | 10.1021/acschemneuro.9b00059 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2197890269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2197890269</sourcerecordid><originalsourceid>FETCH-LOGICAL-a414t-1e007a8a74e1b5edaf1b918780110b283ebd63ae754d74accef9fba577983c7b3</originalsourceid><addsrcrecordid>eNp9UMtOwzAQtBCIlsIfIJQjl8A6L9vHqjylSnAoRxTZzoamSuxiJ4f8PUYtVU9c9qGdmdUMIdcU7igk9F5qr9fYGRycvRMKAHJxQqZUZDxmVKSnR_OEXHi_ASgE8OKcTFIQNClSNiWfqzU6ucWhb3T0bns0fSPbyNZhaUfZNZUNxWD0gKZyTYcuqq2L5t3Y2nD7QhN4KyeN79ejw74xh5tv_CU5q2Xr8WrfZ-Tj6XG1eImXb8-vi_kylhnN-pgiAJNcsgypyrGSNVWCcsaBUlAJT1FVRSqR5VnFMqk11qJWMmdM8FQzlc7I7U536-z3gL4vu8ZrbFtp0A6-TKhgXEBSiADNdlDtrPcO63IbbEk3lhTK32DL42DLfbCBdrP_MKgOqwPpL8kAgB0g0MuNHZwJhv_X_AFXM4sU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2197890269</pqid></control><display><type>article</type><title>Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Inoue, Masamichi ; Ueda, Mitsuharu ; Higashi, Taishi ; Anno, Takayuki ; Fujisawa, Kazuya ; Motoyama, Keiichi ; Mizuguchi, Mineyuki ; Ando, Yukio ; Jono, Hirofumi ; Arima, Hidetoshi</creator><creatorcontrib>Inoue, Masamichi ; Ueda, Mitsuharu ; Higashi, Taishi ; Anno, Takayuki ; Fujisawa, Kazuya ; Motoyama, Keiichi ; Mizuguchi, Mineyuki ; Ando, Yukio ; Jono, Hirofumi ; Arima, Hidetoshi</creatorcontrib><description>Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those processes are urgently needed. In this study, to discover a new drug candidate for ATTR amyloidosis therapy, we focused on polyamidoamine dendrimer (dendrimer), a 3D-structural nanomaterial, which has a branched cationic polymer repeating polyamidoamine units. Dendrimer (G2) not only inhibited ATTR V30M amyloid fibril formation, but also reduced already formed ATTR V30M amyloid fibrils by reducing β-sheet structure of ATTR V30M protein. Moreover, intravenous administration of dendrimer (G2) reduced TTR deposition in human ATTR V30M transgenic rats. These results indicate that dendrimer (G2) may possess both inhibitory and breaking effects on ATTR V30M amyloid, suggesting that dendrimer has the potential as a dual effective agents against TTR amyloidosis.</description><identifier>ISSN: 1948-7193</identifier><identifier>EISSN: 1948-7193</identifier><identifier>DOI: 10.1021/acschemneuro.9b00059</identifier><identifier>PMID: 30912637</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amyloid - drug effects ; Amyloid Neuropathies, Familial - drug therapy ; Animals ; Dendrimers - administration & dosage ; Dendrimers - pharmacology ; Humans ; Polyamines - administration & dosage ; Polyamines - pharmacology ; Rats ; Rats, Transgenic ; Recombinant Proteins ; Thermodynamics</subject><ispartof>ACS chemical neuroscience, 2019-05, Vol.10 (5), p.2584-2590</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a414t-1e007a8a74e1b5edaf1b918780110b283ebd63ae754d74accef9fba577983c7b3</citedby><cites>FETCH-LOGICAL-a414t-1e007a8a74e1b5edaf1b918780110b283ebd63ae754d74accef9fba577983c7b3</cites><orcidid>0000-0001-5498-4234 ; 0000-0002-7977-7597</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acschemneuro.9b00059$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acschemneuro.9b00059$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30912637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inoue, Masamichi</creatorcontrib><creatorcontrib>Ueda, Mitsuharu</creatorcontrib><creatorcontrib>Higashi, Taishi</creatorcontrib><creatorcontrib>Anno, Takayuki</creatorcontrib><creatorcontrib>Fujisawa, Kazuya</creatorcontrib><creatorcontrib>Motoyama, Keiichi</creatorcontrib><creatorcontrib>Mizuguchi, Mineyuki</creatorcontrib><creatorcontrib>Ando, Yukio</creatorcontrib><creatorcontrib>Jono, Hirofumi</creatorcontrib><creatorcontrib>Arima, Hidetoshi</creatorcontrib><title>Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis</title><title>ACS chemical neuroscience</title><addtitle>ACS Chem. Neurosci</addtitle><description>Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those processes are urgently needed. In this study, to discover a new drug candidate for ATTR amyloidosis therapy, we focused on polyamidoamine dendrimer (dendrimer), a 3D-structural nanomaterial, which has a branched cationic polymer repeating polyamidoamine units. Dendrimer (G2) not only inhibited ATTR V30M amyloid fibril formation, but also reduced already formed ATTR V30M amyloid fibrils by reducing β-sheet structure of ATTR V30M protein. Moreover, intravenous administration of dendrimer (G2) reduced TTR deposition in human ATTR V30M transgenic rats. These results indicate that dendrimer (G2) may possess both inhibitory and breaking effects on ATTR V30M amyloid, suggesting that dendrimer has the potential as a dual effective agents against TTR amyloidosis.</description><subject>Amyloid - drug effects</subject><subject>Amyloid Neuropathies, Familial - drug therapy</subject><subject>Animals</subject><subject>Dendrimers - administration & dosage</subject><subject>Dendrimers - pharmacology</subject><subject>Humans</subject><subject>Polyamines - administration & dosage</subject><subject>Polyamines - pharmacology</subject><subject>Rats</subject><subject>Rats, Transgenic</subject><subject>Recombinant Proteins</subject><subject>Thermodynamics</subject><issn>1948-7193</issn><issn>1948-7193</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UMtOwzAQtBCIlsIfIJQjl8A6L9vHqjylSnAoRxTZzoamSuxiJ4f8PUYtVU9c9qGdmdUMIdcU7igk9F5qr9fYGRycvRMKAHJxQqZUZDxmVKSnR_OEXHi_ASgE8OKcTFIQNClSNiWfqzU6ucWhb3T0bns0fSPbyNZhaUfZNZUNxWD0gKZyTYcuqq2L5t3Y2nD7QhN4KyeN79ejw74xh5tv_CU5q2Xr8WrfZ-Tj6XG1eImXb8-vi_kylhnN-pgiAJNcsgypyrGSNVWCcsaBUlAJT1FVRSqR5VnFMqk11qJWMmdM8FQzlc7I7U536-z3gL4vu8ZrbFtp0A6-TKhgXEBSiADNdlDtrPcO63IbbEk3lhTK32DL42DLfbCBdrP_MKgOqwPpL8kAgB0g0MuNHZwJhv_X_AFXM4sU</recordid><startdate>20190515</startdate><enddate>20190515</enddate><creator>Inoue, Masamichi</creator><creator>Ueda, Mitsuharu</creator><creator>Higashi, Taishi</creator><creator>Anno, Takayuki</creator><creator>Fujisawa, Kazuya</creator><creator>Motoyama, Keiichi</creator><creator>Mizuguchi, Mineyuki</creator><creator>Ando, Yukio</creator><creator>Jono, Hirofumi</creator><creator>Arima, Hidetoshi</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5498-4234</orcidid><orcidid>https://orcid.org/0000-0002-7977-7597</orcidid></search><sort><creationdate>20190515</creationdate><title>Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis</title><author>Inoue, Masamichi ; Ueda, Mitsuharu ; Higashi, Taishi ; Anno, Takayuki ; Fujisawa, Kazuya ; Motoyama, Keiichi ; Mizuguchi, Mineyuki ; Ando, Yukio ; Jono, Hirofumi ; Arima, Hidetoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-1e007a8a74e1b5edaf1b918780110b283ebd63ae754d74accef9fba577983c7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Amyloid - drug effects</topic><topic>Amyloid Neuropathies, Familial - drug therapy</topic><topic>Animals</topic><topic>Dendrimers - administration & dosage</topic><topic>Dendrimers - pharmacology</topic><topic>Humans</topic><topic>Polyamines - administration & dosage</topic><topic>Polyamines - pharmacology</topic><topic>Rats</topic><topic>Rats, Transgenic</topic><topic>Recombinant Proteins</topic><topic>Thermodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inoue, Masamichi</creatorcontrib><creatorcontrib>Ueda, Mitsuharu</creatorcontrib><creatorcontrib>Higashi, Taishi</creatorcontrib><creatorcontrib>Anno, Takayuki</creatorcontrib><creatorcontrib>Fujisawa, Kazuya</creatorcontrib><creatorcontrib>Motoyama, Keiichi</creatorcontrib><creatorcontrib>Mizuguchi, Mineyuki</creatorcontrib><creatorcontrib>Ando, Yukio</creatorcontrib><creatorcontrib>Jono, Hirofumi</creatorcontrib><creatorcontrib>Arima, Hidetoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>ACS chemical neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inoue, Masamichi</au><au>Ueda, Mitsuharu</au><au>Higashi, Taishi</au><au>Anno, Takayuki</au><au>Fujisawa, Kazuya</au><au>Motoyama, Keiichi</au><au>Mizuguchi, Mineyuki</au><au>Ando, Yukio</au><au>Jono, Hirofumi</au><au>Arima, Hidetoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis</atitle><jtitle>ACS chemical neuroscience</jtitle><addtitle>ACS Chem. Neurosci</addtitle><date>2019-05-15</date><risdate>2019</risdate><volume>10</volume><issue>5</issue><spage>2584</spage><epage>2590</epage><pages>2584-2590</pages><issn>1948-7193</issn><eissn>1948-7193</eissn><abstract>Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those processes are urgently needed. In this study, to discover a new drug candidate for ATTR amyloidosis therapy, we focused on polyamidoamine dendrimer (dendrimer), a 3D-structural nanomaterial, which has a branched cationic polymer repeating polyamidoamine units. Dendrimer (G2) not only inhibited ATTR V30M amyloid fibril formation, but also reduced already formed ATTR V30M amyloid fibrils by reducing β-sheet structure of ATTR V30M protein. Moreover, intravenous administration of dendrimer (G2) reduced TTR deposition in human ATTR V30M transgenic rats. These results indicate that dendrimer (G2) may possess both inhibitory and breaking effects on ATTR V30M amyloid, suggesting that dendrimer has the potential as a dual effective agents against TTR amyloidosis.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>30912637</pmid><doi>10.1021/acschemneuro.9b00059</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-5498-4234</orcidid><orcidid>https://orcid.org/0000-0002-7977-7597</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1948-7193 |
| ispartof | ACS chemical neuroscience, 2019-05, Vol.10 (5), p.2584-2590 |
| issn | 1948-7193 1948-7193 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2197890269 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Amyloid - drug effects Amyloid Neuropathies, Familial - drug therapy Animals Dendrimers - administration & dosage Dendrimers - pharmacology Humans Polyamines - administration & dosage Polyamines - pharmacology Rats Rats, Transgenic Recombinant Proteins Thermodynamics |
| title | Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T11%3A32%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Therapeutic%20Potential%20of%20Polyamidoamine%20Dendrimer%20for%20Amyloidogenic%20Transthyretin%20Amyloidosis&rft.jtitle=ACS%20chemical%20neuroscience&rft.au=Inoue,%20Masamichi&rft.date=2019-05-15&rft.volume=10&rft.issue=5&rft.spage=2584&rft.epage=2590&rft.pages=2584-2590&rft.issn=1948-7193&rft.eissn=1948-7193&rft_id=info:doi/10.1021/acschemneuro.9b00059&rft_dat=%3Cproquest_cross%3E2197890269%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2197890269&rft_id=info:pmid/30912637&rfr_iscdi=true |