Supramolecular Modulation of Structural Polymorphism in Pathogenic α‐Synuclein Fibrils Using Copper(II) Coordination
Structural variation of α‐synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils with pathologic features. Herein, we demonstrate Cu(II)‐based supramolecular approach for unraveling the for...
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| Veröffentlicht in: | Angewandte Chemie 2018-03, Vol.130 (12), p.3153-3157 |
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| creator | Choi, Tae Su Lee, Jeeyoung Han, Jong Yoon Jung, Byung Chul Wongkongkathep, Piriya Loo, Joseph A. Lee, Min Jae Kim, Hugh I. |
| description | Structural variation of α‐synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils with pathologic features. Herein, we demonstrate Cu(II)‐based supramolecular approach for unraveling the formation process of pathogenic αSyn fibrils and its application in a neurotoxic mechanism study. The conformation of αSyn monomer was strained by macrochelation with Cu(II), thereby disrupting the fibril elongation while promoting its nucleation. This non‐canonical process formed shortened, β‐sheet enriched αSyn fibrils ( |
| doi_str_mv | 10.1002/ange.201712286 |
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Anders als bei der normalen α‐Synuclein(αSyn)‐Fibrillenbildung vermittelt Kupfer(II) eine αSyn‐Keimbildung, verzögert aber das Wachstum. Infolge dieses Mechanismus entstehen hoch zellgängige und neurotoxische Fibrillen. Diese unübliche αSyn‐Selbstorganisation schafft eine supramolekulare Grundlage für die Erzeugung pathogener Amyloid‐Aggregate.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.201712286</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>Brain ; Cell death ; Chemistry ; Conformation ; Copper ; Copper compounds ; Elongation ; Etiology ; Fibrillen ; Fibrillogenesis ; Kleinwinkel-Röntgenstreuung ; Massenspektrometrie ; Neurotoxicity ; Parkinson-Krankheit ; Physiological effects ; Physiological factors ; Polymorphism ; Synuclein ; Übergangsmetalle</subject><ispartof>Angewandte Chemie, 2018-03, Vol.130 (12), p.3153-3157</ispartof><rights>2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1896-e1efec2955c449c7a11bc88a56c171580d6151777de382cae7b0fc2688e874883</citedby><cites>FETCH-LOGICAL-c1896-e1efec2955c449c7a11bc88a56c171580d6151777de382cae7b0fc2688e874883</cites><orcidid>0000-0001-9205-1806 ; 0000-0002-1515-3275 ; 0000000215153275 ; 0000000192051806</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.201712286$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.201712286$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.osti.gov/biblio/1421570$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Tae Su</creatorcontrib><creatorcontrib>Lee, Jeeyoung</creatorcontrib><creatorcontrib>Han, Jong Yoon</creatorcontrib><creatorcontrib>Jung, Byung Chul</creatorcontrib><creatorcontrib>Wongkongkathep, Piriya</creatorcontrib><creatorcontrib>Loo, Joseph A.</creatorcontrib><creatorcontrib>Lee, Min Jae</creatorcontrib><creatorcontrib>Kim, Hugh I.</creatorcontrib><title>Supramolecular Modulation of Structural Polymorphism in Pathogenic α‐Synuclein Fibrils Using Copper(II) Coordination</title><title>Angewandte Chemie</title><description>Structural variation of α‐synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils with pathologic features. Herein, we demonstrate Cu(II)‐based supramolecular approach for unraveling the formation process of pathogenic αSyn fibrils and its application in a neurotoxic mechanism study. The conformation of αSyn monomer was strained by macrochelation with Cu(II), thereby disrupting the fibril elongation while promoting its nucleation. This non‐canonical process formed shortened, β‐sheet enriched αSyn fibrils (<0.2 μm) that were rapidly transmitted and accumulated to neuronal cells, causing neuronal cell death, in sharp contrast to typical αSyn fibrils (ca. 1 μm). Our approach provided the supramolecular basis for the formation of pathogenic fibrils through physiological factors, such as brain Cu(II).
Anders als bei der normalen α‐Synuclein(αSyn)‐Fibrillenbildung vermittelt Kupfer(II) eine αSyn‐Keimbildung, verzögert aber das Wachstum. Infolge dieses Mechanismus entstehen hoch zellgängige und neurotoxische Fibrillen. Diese unübliche αSyn‐Selbstorganisation schafft eine supramolekulare Grundlage für die Erzeugung pathogener Amyloid‐Aggregate.</description><subject>Brain</subject><subject>Cell death</subject><subject>Chemistry</subject><subject>Conformation</subject><subject>Copper</subject><subject>Copper compounds</subject><subject>Elongation</subject><subject>Etiology</subject><subject>Fibrillen</subject><subject>Fibrillogenesis</subject><subject>Kleinwinkel-Röntgenstreuung</subject><subject>Massenspektrometrie</subject><subject>Neurotoxicity</subject><subject>Parkinson-Krankheit</subject><subject>Physiological effects</subject><subject>Physiological factors</subject><subject>Polymorphism</subject><subject>Synuclein</subject><subject>Übergangsmetalle</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkc9uEzEQxi1EJULhytmCCxw2eLx_7D1WUVsiFagUeracyWziamMv9q6q3HiEvkpfhIfgSXAJgmNPM9L8vk8z8zH2BsQchJAfrd_SXApQIKVunrEZ1BKKUtXqOZsJUVWFllX7gr1M6VYI0UjVztjdahqi3YeecOpt5J_DJtfRBc9Dx1djnHCcou35degP-xCHnUt77jy_tuMubMk75D8ffv24Xx38hD3lyYVbR9cnfpOc3_JFGAaK75fLD7kNceP8H_dX7KSzfaLXf-spu7k4_7b4VFx9vVwuzq4KBN02BQF1hLKta6yqFpUFWKPWtm4w31lrsWmgBqXUhkot0ZJaiw5lozVpVWldnrK3R9-QRmcSupFwh8F7wtFAJaFWIkPvjtAQw_eJ0mhuwxR93svkf0IJZVXKTM2PFMaQUqTODNHtbTwYEOYxAfOYgPmXQBa0R8Gd6-nwBG3Ovlye_9f-Br-yjNA</recordid><startdate>20180312</startdate><enddate>20180312</enddate><creator>Choi, Tae Su</creator><creator>Lee, Jeeyoung</creator><creator>Han, Jong Yoon</creator><creator>Jung, Byung Chul</creator><creator>Wongkongkathep, Piriya</creator><creator>Loo, Joseph A.</creator><creator>Lee, Min Jae</creator><creator>Kim, Hugh I.</creator><general>Wiley Subscription Services, Inc</general><general>Wiley Blackwell (John Wiley & Sons)</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0001-9205-1806</orcidid><orcidid>https://orcid.org/0000-0002-1515-3275</orcidid><orcidid>https://orcid.org/0000000215153275</orcidid><orcidid>https://orcid.org/0000000192051806</orcidid></search><sort><creationdate>20180312</creationdate><title>Supramolecular Modulation of Structural Polymorphism in Pathogenic α‐Synuclein Fibrils Using Copper(II) Coordination</title><author>Choi, Tae Su ; Lee, Jeeyoung ; Han, Jong Yoon ; Jung, Byung Chul ; Wongkongkathep, Piriya ; Loo, Joseph A. ; Lee, Min Jae ; Kim, Hugh I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1896-e1efec2955c449c7a11bc88a56c171580d6151777de382cae7b0fc2688e874883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Brain</topic><topic>Cell death</topic><topic>Chemistry</topic><topic>Conformation</topic><topic>Copper</topic><topic>Copper compounds</topic><topic>Elongation</topic><topic>Etiology</topic><topic>Fibrillen</topic><topic>Fibrillogenesis</topic><topic>Kleinwinkel-Röntgenstreuung</topic><topic>Massenspektrometrie</topic><topic>Neurotoxicity</topic><topic>Parkinson-Krankheit</topic><topic>Physiological effects</topic><topic>Physiological factors</topic><topic>Polymorphism</topic><topic>Synuclein</topic><topic>Übergangsmetalle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Tae Su</creatorcontrib><creatorcontrib>Lee, Jeeyoung</creatorcontrib><creatorcontrib>Han, Jong Yoon</creatorcontrib><creatorcontrib>Jung, Byung Chul</creatorcontrib><creatorcontrib>Wongkongkathep, Piriya</creatorcontrib><creatorcontrib>Loo, Joseph A.</creatorcontrib><creatorcontrib>Lee, Min Jae</creatorcontrib><creatorcontrib>Kim, Hugh I.</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>OSTI.GOV</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Tae Su</au><au>Lee, Jeeyoung</au><au>Han, Jong Yoon</au><au>Jung, Byung Chul</au><au>Wongkongkathep, Piriya</au><au>Loo, Joseph A.</au><au>Lee, Min Jae</au><au>Kim, Hugh I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Supramolecular Modulation of Structural Polymorphism in Pathogenic α‐Synuclein Fibrils Using Copper(II) Coordination</atitle><jtitle>Angewandte Chemie</jtitle><date>2018-03-12</date><risdate>2018</risdate><volume>130</volume><issue>12</issue><spage>3153</spage><epage>3157</epage><pages>3153-3157</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>Structural variation of α‐synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils with pathologic features. Herein, we demonstrate Cu(II)‐based supramolecular approach for unraveling the formation process of pathogenic αSyn fibrils and its application in a neurotoxic mechanism study. The conformation of αSyn monomer was strained by macrochelation with Cu(II), thereby disrupting the fibril elongation while promoting its nucleation. This non‐canonical process formed shortened, β‐sheet enriched αSyn fibrils (<0.2 μm) that were rapidly transmitted and accumulated to neuronal cells, causing neuronal cell death, in sharp contrast to typical αSyn fibrils (ca. 1 μm). Our approach provided the supramolecular basis for the formation of pathogenic fibrils through physiological factors, such as brain Cu(II).
Anders als bei der normalen α‐Synuclein(αSyn)‐Fibrillenbildung vermittelt Kupfer(II) eine αSyn‐Keimbildung, verzögert aber das Wachstum. Infolge dieses Mechanismus entstehen hoch zellgängige und neurotoxische Fibrillen. Diese unübliche αSyn‐Selbstorganisation schafft eine supramolekulare Grundlage für die Erzeugung pathogener Amyloid‐Aggregate.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ange.201712286</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-9205-1806</orcidid><orcidid>https://orcid.org/0000-0002-1515-3275</orcidid><orcidid>https://orcid.org/0000000215153275</orcidid><orcidid>https://orcid.org/0000000192051806</orcidid></addata></record> |
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| subjects | Brain Cell death Chemistry Conformation Copper Copper compounds Elongation Etiology Fibrillen Fibrillogenesis Kleinwinkel-Röntgenstreuung Massenspektrometrie Neurotoxicity Parkinson-Krankheit Physiological effects Physiological factors Polymorphism Synuclein Übergangsmetalle |
| title | Supramolecular Modulation of Structural Polymorphism in Pathogenic α‐Synuclein Fibrils Using Copper(II) Coordination |
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