Hepta-Histidine Inhibits Tau Aggregation
Tau aggregation is a central hallmark of tauopathies such as frontotemporal lobar degeneration and progressive supranuclear palsy as well as of Alzheimer’s disease, and it has been a target for therapeutic development. Herein, we unexpectedly found that hepta-histidine (7H), an inhibitor of the inte...
Gespeichert in:
| Veröffentlicht in: | ACS chemical neuroscience 2021-08, Vol.12 (16), p.3015-3027 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3027 |
|---|---|
| container_issue | 16 |
| container_start_page | 3015 |
| container_title | ACS chemical neuroscience |
| container_volume | 12 |
| creator | Kondo, Kanoh Ikura, Teikichi Tanaka, Hikari Fujita, Kyota Takayama, Sumire Yoshioka, Yuki Tagawa, Kazuhiko Homma, Hidenori Liu, Su Kawasaki, Ryosuke Huang, Yong Ito, Nobutoshi Tate, Shin-ichi Okazawa, Hitoshi |
| description | Tau aggregation is a central hallmark of tauopathies such as frontotemporal lobar degeneration and progressive supranuclear palsy as well as of Alzheimer’s disease, and it has been a target for therapeutic development. Herein, we unexpectedly found that hepta-histidine (7H), an inhibitor of the interaction between Ku70 and Huntingtin proteins, suppresses aggregation of Tau-R3 peptides in vitro. Addition of the trans-activator of transcription (TAT) sequence (YGRKKRRQRRR) derived from the TAT protein to 7H increased its permeability into cells, and TAT-7H treatment of iPS cell-derived neurons carrying Tau or APP mutations suppressed Tau phosphorylation. These results indicate that 7H is a promising lead compound for developing anti-aggregation drugs against Tau-related neurodegenerative diseases including Alzheimer’s disease (AD). |
| doi_str_mv | 10.1021/acschemneuro.1c00164 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2555973208</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2555973208</sourcerecordid><originalsourceid>FETCH-LOGICAL-a325t-5f22e5f9cfb74041f0ea8a7e4bd75835af1976dd1ecbac572ea11de8c683166d3</originalsourceid><addsrcrecordid>eNp9kD1vwjAQhq2qlUpp_0EHRpZQnxN_ZESoLUhIXehsXZwzGEFC7WTov28qGJiY7pXufU66h7FX4DPgAt7QJbejY0N9bGfgOAdV3LERlIXJNJT5_VV-ZE8p7TlXJTdqxKZLOnWYLUPqQh0amqyaXahClyYb7Cfz7TbSFrvQNs_sweMh0ctljtn3x_tmsczWX5-rxXydYS5kl0kvBElfOl_pghfgOaFBTUVVa2lyiR5KreoayFXopBaEADUZp0wOStX5mE3Pd0-x_ekpdfYYkqPDARtq-2SFlLLUueBmqBbnqottSpG8PcVwxPhrgdt_MfZajL2IGTB-xoat3bd9bIZ_biN_0Chqcw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2555973208</pqid></control><display><type>article</type><title>Hepta-Histidine Inhibits Tau Aggregation</title><source>American Chemical Society Journals</source><creator>Kondo, Kanoh ; Ikura, Teikichi ; Tanaka, Hikari ; Fujita, Kyota ; Takayama, Sumire ; Yoshioka, Yuki ; Tagawa, Kazuhiko ; Homma, Hidenori ; Liu, Su ; Kawasaki, Ryosuke ; Huang, Yong ; Ito, Nobutoshi ; Tate, Shin-ichi ; Okazawa, Hitoshi</creator><creatorcontrib>Kondo, Kanoh ; Ikura, Teikichi ; Tanaka, Hikari ; Fujita, Kyota ; Takayama, Sumire ; Yoshioka, Yuki ; Tagawa, Kazuhiko ; Homma, Hidenori ; Liu, Su ; Kawasaki, Ryosuke ; Huang, Yong ; Ito, Nobutoshi ; Tate, Shin-ichi ; Okazawa, Hitoshi</creatorcontrib><description>Tau aggregation is a central hallmark of tauopathies such as frontotemporal lobar degeneration and progressive supranuclear palsy as well as of Alzheimer’s disease, and it has been a target for therapeutic development. Herein, we unexpectedly found that hepta-histidine (7H), an inhibitor of the interaction between Ku70 and Huntingtin proteins, suppresses aggregation of Tau-R3 peptides in vitro. Addition of the trans-activator of transcription (TAT) sequence (YGRKKRRQRRR) derived from the TAT protein to 7H increased its permeability into cells, and TAT-7H treatment of iPS cell-derived neurons carrying Tau or APP mutations suppressed Tau phosphorylation. These results indicate that 7H is a promising lead compound for developing anti-aggregation drugs against Tau-related neurodegenerative diseases including Alzheimer’s disease (AD).</description><identifier>ISSN: 1948-7193</identifier><identifier>EISSN: 1948-7193</identifier><identifier>DOI: 10.1021/acschemneuro.1c00164</identifier><language>eng</language><publisher>American Chemical Society</publisher><ispartof>ACS chemical neuroscience, 2021-08, Vol.12 (16), p.3015-3027</ispartof><rights>2021 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a325t-5f22e5f9cfb74041f0ea8a7e4bd75835af1976dd1ecbac572ea11de8c683166d3</citedby><cites>FETCH-LOGICAL-a325t-5f22e5f9cfb74041f0ea8a7e4bd75835af1976dd1ecbac572ea11de8c683166d3</cites><orcidid>0000-0002-6127-5046</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.1c00164$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acschemneuro.1c00164$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27074,27922,27923,56736,56786</link.rule.ids></links><search><creatorcontrib>Kondo, Kanoh</creatorcontrib><creatorcontrib>Ikura, Teikichi</creatorcontrib><creatorcontrib>Tanaka, Hikari</creatorcontrib><creatorcontrib>Fujita, Kyota</creatorcontrib><creatorcontrib>Takayama, Sumire</creatorcontrib><creatorcontrib>Yoshioka, Yuki</creatorcontrib><creatorcontrib>Tagawa, Kazuhiko</creatorcontrib><creatorcontrib>Homma, Hidenori</creatorcontrib><creatorcontrib>Liu, Su</creatorcontrib><creatorcontrib>Kawasaki, Ryosuke</creatorcontrib><creatorcontrib>Huang, Yong</creatorcontrib><creatorcontrib>Ito, Nobutoshi</creatorcontrib><creatorcontrib>Tate, Shin-ichi</creatorcontrib><creatorcontrib>Okazawa, Hitoshi</creatorcontrib><title>Hepta-Histidine Inhibits Tau Aggregation</title><title>ACS chemical neuroscience</title><addtitle>ACS Chem. Neurosci</addtitle><description>Tau aggregation is a central hallmark of tauopathies such as frontotemporal lobar degeneration and progressive supranuclear palsy as well as of Alzheimer’s disease, and it has been a target for therapeutic development. Herein, we unexpectedly found that hepta-histidine (7H), an inhibitor of the interaction between Ku70 and Huntingtin proteins, suppresses aggregation of Tau-R3 peptides in vitro. Addition of the trans-activator of transcription (TAT) sequence (YGRKKRRQRRR) derived from the TAT protein to 7H increased its permeability into cells, and TAT-7H treatment of iPS cell-derived neurons carrying Tau or APP mutations suppressed Tau phosphorylation. These results indicate that 7H is a promising lead compound for developing anti-aggregation drugs against Tau-related neurodegenerative diseases including Alzheimer’s disease (AD).</description><issn>1948-7193</issn><issn>1948-7193</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kD1vwjAQhq2qlUpp_0EHRpZQnxN_ZESoLUhIXehsXZwzGEFC7WTov28qGJiY7pXufU66h7FX4DPgAt7QJbejY0N9bGfgOAdV3LERlIXJNJT5_VV-ZE8p7TlXJTdqxKZLOnWYLUPqQh0amqyaXahClyYb7Cfz7TbSFrvQNs_sweMh0ctljtn3x_tmsczWX5-rxXydYS5kl0kvBElfOl_pghfgOaFBTUVVa2lyiR5KreoayFXopBaEADUZp0wOStX5mE3Pd0-x_ekpdfYYkqPDARtq-2SFlLLUueBmqBbnqottSpG8PcVwxPhrgdt_MfZajL2IGTB-xoat3bd9bIZ_biN_0Chqcw</recordid><startdate>20210818</startdate><enddate>20210818</enddate><creator>Kondo, Kanoh</creator><creator>Ikura, Teikichi</creator><creator>Tanaka, Hikari</creator><creator>Fujita, Kyota</creator><creator>Takayama, Sumire</creator><creator>Yoshioka, Yuki</creator><creator>Tagawa, Kazuhiko</creator><creator>Homma, Hidenori</creator><creator>Liu, Su</creator><creator>Kawasaki, Ryosuke</creator><creator>Huang, Yong</creator><creator>Ito, Nobutoshi</creator><creator>Tate, Shin-ichi</creator><creator>Okazawa, Hitoshi</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6127-5046</orcidid></search><sort><creationdate>20210818</creationdate><title>Hepta-Histidine Inhibits Tau Aggregation</title><author>Kondo, Kanoh ; Ikura, Teikichi ; Tanaka, Hikari ; Fujita, Kyota ; Takayama, Sumire ; Yoshioka, Yuki ; Tagawa, Kazuhiko ; Homma, Hidenori ; Liu, Su ; Kawasaki, Ryosuke ; Huang, Yong ; Ito, Nobutoshi ; Tate, Shin-ichi ; Okazawa, Hitoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a325t-5f22e5f9cfb74041f0ea8a7e4bd75835af1976dd1ecbac572ea11de8c683166d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kondo, Kanoh</creatorcontrib><creatorcontrib>Ikura, Teikichi</creatorcontrib><creatorcontrib>Tanaka, Hikari</creatorcontrib><creatorcontrib>Fujita, Kyota</creatorcontrib><creatorcontrib>Takayama, Sumire</creatorcontrib><creatorcontrib>Yoshioka, Yuki</creatorcontrib><creatorcontrib>Tagawa, Kazuhiko</creatorcontrib><creatorcontrib>Homma, Hidenori</creatorcontrib><creatorcontrib>Liu, Su</creatorcontrib><creatorcontrib>Kawasaki, Ryosuke</creatorcontrib><creatorcontrib>Huang, Yong</creatorcontrib><creatorcontrib>Ito, Nobutoshi</creatorcontrib><creatorcontrib>Tate, Shin-ichi</creatorcontrib><creatorcontrib>Okazawa, Hitoshi</creatorcontrib><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>Kondo, Kanoh</au><au>Ikura, Teikichi</au><au>Tanaka, Hikari</au><au>Fujita, Kyota</au><au>Takayama, Sumire</au><au>Yoshioka, Yuki</au><au>Tagawa, Kazuhiko</au><au>Homma, Hidenori</au><au>Liu, Su</au><au>Kawasaki, Ryosuke</au><au>Huang, Yong</au><au>Ito, Nobutoshi</au><au>Tate, Shin-ichi</au><au>Okazawa, Hitoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepta-Histidine Inhibits Tau Aggregation</atitle><jtitle>ACS chemical neuroscience</jtitle><addtitle>ACS Chem. Neurosci</addtitle><date>2021-08-18</date><risdate>2021</risdate><volume>12</volume><issue>16</issue><spage>3015</spage><epage>3027</epage><pages>3015-3027</pages><issn>1948-7193</issn><eissn>1948-7193</eissn><abstract>Tau aggregation is a central hallmark of tauopathies such as frontotemporal lobar degeneration and progressive supranuclear palsy as well as of Alzheimer’s disease, and it has been a target for therapeutic development. Herein, we unexpectedly found that hepta-histidine (7H), an inhibitor of the interaction between Ku70 and Huntingtin proteins, suppresses aggregation of Tau-R3 peptides in vitro. Addition of the trans-activator of transcription (TAT) sequence (YGRKKRRQRRR) derived from the TAT protein to 7H increased its permeability into cells, and TAT-7H treatment of iPS cell-derived neurons carrying Tau or APP mutations suppressed Tau phosphorylation. These results indicate that 7H is a promising lead compound for developing anti-aggregation drugs against Tau-related neurodegenerative diseases including Alzheimer’s disease (AD).</abstract><pub>American Chemical Society</pub><doi>10.1021/acschemneuro.1c00164</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6127-5046</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1948-7193 |
| ispartof | ACS chemical neuroscience, 2021-08, Vol.12 (16), p.3015-3027 |
| issn | 1948-7193 1948-7193 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2555973208 |
| source | American Chemical Society Journals |
| title | Hepta-Histidine Inhibits Tau Aggregation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T12%3A42%3A17IST&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=Hepta-Histidine%20Inhibits%20Tau%20Aggregation&rft.jtitle=ACS%20chemical%20neuroscience&rft.au=Kondo,%20Kanoh&rft.date=2021-08-18&rft.volume=12&rft.issue=16&rft.spage=3015&rft.epage=3027&rft.pages=3015-3027&rft.issn=1948-7193&rft.eissn=1948-7193&rft_id=info:doi/10.1021/acschemneuro.1c00164&rft_dat=%3Cproquest_cross%3E2555973208%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=2555973208&rft_id=info:pmid/&rfr_iscdi=true |