Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.
Identifieur interne : 000048 ( Main/Corpus ); précédent : 000047; suivant : 000049Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.
Auteurs : M Grazia Cotticelli ; Roberto Forestieri ; Shujuan Xia ; Sipak Joyasawal ; Taehee Lee ; Kexin Xu ; Amos B. Smith Iii ; Donna M. Huryn ; Robert B. WilsonSource :
- ACS chemical neuroscience [ 1948-7193 ] ; 2020.
Abstract
Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder for which there is no cure or approved treatment. It is characterized by the loss or impaired activity of frataxin protein, which is involved in the biogenesis of iron-sulfur clusters. Our previous studies suggested that cell death in FRDA may involve ferroptosis, an iron-dependent form of cell death requiring lipid peroxidation. Based on reports that oleic acid acts as a ferroptosis inhibitor, we evaluated whether it, other fatty acids, and fatty acid derivatives could rescue viability in cellular models of FRDA. We identified a trifluoromethyl alcohol analog of oleic acid that was significantly more potent than oleic acid itself. Further evaluation indicated that the effects were stereoselective, although a specific molecular target has not yet been identified. This work provides a potential starting point for therapeutics to treat FRDA, as well as a valuable probe molecule to interrogate FRDA pathophysiology.
DOI: 10.1021/acschemneuro.0c00323
PubMed: 32786299
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.</title><author><name sortKey="Cotticelli, M Grazia" sort="Cotticelli, M Grazia" uniqKey="Cotticelli M" first="M Grazia" last="Cotticelli">M Grazia Cotticelli</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Forestieri, Roberto" sort="Forestieri, Roberto" uniqKey="Forestieri R" first="Roberto" last="Forestieri">Roberto Forestieri</name><affiliation><nlm:affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Xia, Shujuan" sort="Xia, Shujuan" uniqKey="Xia S" first="Shujuan" last="Xia">Shujuan Xia</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Joyasawal, Sipak" sort="Joyasawal, Sipak" uniqKey="Joyasawal S" first="Sipak" last="Joyasawal">Sipak Joyasawal</name><affiliation><nlm:affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Taehee" sort="Lee, Taehee" uniqKey="Lee T" first="Taehee" last="Lee">Taehee Lee</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Xu, Kexin" sort="Xu, Kexin" uniqKey="Xu K" first="Kexin" last="Xu">Kexin Xu</name><affiliation><nlm:affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Smith Iii, Amos B" sort="Smith Iii, Amos B" uniqKey="Smith Iii A" first="Amos B" last="Smith Iii">Amos B. Smith Iii</name><affiliation><nlm:affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Huryn, Donna M" sort="Huryn, Donna M" uniqKey="Huryn D" first="Donna M" last="Huryn">Donna M. Huryn</name><affiliation><nlm:affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Wilson, Robert B" sort="Wilson, Robert B" uniqKey="Wilson R" first="Robert B" last="Wilson">Robert B. Wilson</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32786299</idno><idno type="pmid">32786299</idno><idno type="doi">10.1021/acschemneuro.0c00323</idno><idno type="wicri:Area/Main/Corpus">000048</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000048</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.</title><author><name sortKey="Cotticelli, M Grazia" sort="Cotticelli, M Grazia" uniqKey="Cotticelli M" first="M Grazia" last="Cotticelli">M Grazia Cotticelli</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Forestieri, Roberto" sort="Forestieri, Roberto" uniqKey="Forestieri R" first="Roberto" last="Forestieri">Roberto Forestieri</name><affiliation><nlm:affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Xia, Shujuan" sort="Xia, Shujuan" uniqKey="Xia S" first="Shujuan" last="Xia">Shujuan Xia</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Joyasawal, Sipak" sort="Joyasawal, Sipak" uniqKey="Joyasawal S" first="Sipak" last="Joyasawal">Sipak Joyasawal</name><affiliation><nlm:affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Taehee" sort="Lee, Taehee" uniqKey="Lee T" first="Taehee" last="Lee">Taehee Lee</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Xu, Kexin" sort="Xu, Kexin" uniqKey="Xu K" first="Kexin" last="Xu">Kexin Xu</name><affiliation><nlm:affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Smith Iii, Amos B" sort="Smith Iii, Amos B" uniqKey="Smith Iii A" first="Amos B" last="Smith Iii">Amos B. Smith Iii</name><affiliation><nlm:affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Huryn, Donna M" sort="Huryn, Donna M" uniqKey="Huryn D" first="Donna M" last="Huryn">Donna M. Huryn</name><affiliation><nlm:affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Wilson, Robert B" sort="Wilson, Robert B" uniqKey="Wilson R" first="Robert B" last="Wilson">Robert B. Wilson</name><affiliation><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</nlm:affiliation></affiliation></author></analytic><series><title level="j">ACS chemical neuroscience</title><idno type="eISSN">1948-7193</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">Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder for which there is no cure or approved treatment. It is characterized by the loss or impaired activity of frataxin protein, which is involved in the biogenesis of iron-sulfur clusters. Our previous studies suggested that cell death in FRDA may involve ferroptosis, an iron-dependent form of cell death requiring lipid peroxidation. Based on reports that oleic acid acts as a ferroptosis inhibitor, we evaluated whether it, other fatty acids, and fatty acid derivatives could rescue viability in cellular models of FRDA. We identified a trifluoromethyl alcohol analog of oleic acid that was significantly more potent than oleic acid itself. Further evaluation indicated that the effects were stereoselective, although a specific molecular target has not yet been identified. This work provides a potential starting point for therapeutics to treat FRDA, as well as a valuable probe molecule to interrogate FRDA pathophysiology.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32786299</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>14</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1948-7193</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>17</Issue><PubDate><Year>2020</Year><Month>09</Month><Day>02</Day></PubDate></JournalIssue><Title>ACS chemical neuroscience</Title><ISOAbbreviation>ACS Chem Neurosci</ISOAbbreviation></Journal><ArticleTitle>Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.</ArticleTitle><Pagination><MedlinePgn>2535-2542</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acschemneuro.0c00323</ELocationID><Abstract><AbstractText>Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder for which there is no cure or approved treatment. It is characterized by the loss or impaired activity of frataxin protein, which is involved in the biogenesis of iron-sulfur clusters. Our previous studies suggested that cell death in FRDA may involve ferroptosis, an iron-dependent form of cell death requiring lipid peroxidation. Based on reports that oleic acid acts as a ferroptosis inhibitor, we evaluated whether it, other fatty acids, and fatty acid derivatives could rescue viability in cellular models of FRDA. We identified a trifluoromethyl alcohol analog of oleic acid that was significantly more potent than oleic acid itself. Further evaluation indicated that the effects were stereoselective, although a specific molecular target has not yet been identified. This work provides a potential starting point for therapeutics to treat FRDA, as well as a valuable probe molecule to interrogate FRDA pathophysiology.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cotticelli</LastName><ForeName>M Grazia</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Forestieri</LastName><ForeName>Roberto</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xia</LastName><ForeName>Shujuan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joyasawal</LastName><ForeName>Sipak</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-6255-8833</Identifier><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Taehee</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Kexin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith Iii</LastName><ForeName>Amos B</ForeName><Initials>AB</Initials><Identifier Source="ORCID">0000-0002-1712-8567</Identifier><AffiliationInfo><Affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huryn</LastName><ForeName>Donna M</ForeName><Initials>DM</Initials><Identifier Source="ORCID">0000-0001-5542-4968</Identifier><AffiliationInfo><Affiliation>Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wilson</LastName><ForeName>Robert B</ForeName><Initials>RB</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>08</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>ACS Chem Neurosci</MedlineTA><NlmUniqueID>101525337</NlmUniqueID><ISSNLinking>1948-7193</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Friedreich ataxia</Keyword><Keyword MajorTopicYN="Y">carboxylic acid isostere</Keyword><Keyword MajorTopicYN="Y">ferroptosis</Keyword><Keyword MajorTopicYN="Y">lipid peroxidation</Keyword><Keyword MajorTopicYN="Y">oleic acid</Keyword><Keyword MajorTopicYN="Y">trifluoromethyl alcohol</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32786299</ArticleId><ArticleId IdType="doi">10.1021/acschemneuro.0c00323</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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