Treatment-resistant schizophrenia: focus on the transsulfuration pathway.
Identifieur interne : 000008 ( Main/Exploration ); précédent : 000007; suivant : 000009Treatment-resistant schizophrenia: focus on the transsulfuration pathway.
Auteurs : Thomas Berry [Australie] ; Eid Abohamza [Qatar] ; Ahmed A. Moustafa [Australie]Source :
- Reviews in the neurosciences [ 0334-1763 ] ; 2020.
Abstract
Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. The severity of illness is positively related to homocysteine levels, with high homocysteine levels due to the low activity of the transsulfuration pathway, which metabolizes homocysteine in synthesizing L-cysteine. Glutathione levels are low in schizophrenia, which indicates shortages of L-cysteine and low activity of the transsulfuration pathway. Hydrogen sulfide (H2S) levels are low in schizophrenia. H2S is synthesized by cystathionine β-synthase and cystathionine γ-lyase, which are the two enzymes in the transsulfuration pathway. Iron-sulfur proteins obtain sulfur from L-cysteine. The oxidative phosphorylation (OXPHOS) pathway has various iron-sulfur proteins. With low levels of L-cysteine, iron-sulfur cluster formation will be dysregulated leading to deficits in OXPHOS in schizophrenia. Molybdenum cofactor (MoCo) synthesis requires sulfur, which is obtained from L-cysteine. With low levels of MoCo synthesis, molybdenum-dependent sulfite oxidase (SUOX) will not be synthesized at appropriate levels. SUOX detoxifies sulfite from sulfur-containing amino acids. If sulfites are not detoxified, there can be sulfite toxicity. The transsulfuration pathway metabolizes selenomethionine, whereby selenium from selenomethionine can be used for selenoprotein synthesis. The low activity of the transsulfuration pathway decreases selenoprotein synthesis. Glutathione peroxidase (GPX), with various GPXs being selenoprotein, is low in schizophrenia. The dysregulations of selenoproteins would lead to oxidant stress, which would increase the methylation of genes and histones leading to epigenetic changes in TRS. An add-on treatment to mainline antipsychotics is proposed for TRS that targets the dysregulations of the transsulfuration pathway and the dysregulations of other pathways stemming from the transsulfuration pathway being dysregulated.
DOI: 10.1515/revneuro-2019-0057
PubMed: 31714892
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Box 2713, Doha, Qatar.</nlm:affiliation><country xml:lang="fr">Qatar</country><wicri:regionArea>Department of Social Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha</wicri:regionArea><wicri:noRegion>Doha</wicri:noRegion></affiliation></author><author><name sortKey="Moustafa, Ahmed A" sort="Moustafa, Ahmed A" uniqKey="Moustafa A" first="Ahmed A" last="Moustafa">Ahmed A. 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Moustafa</name><affiliation wicri:level="1"><nlm:affiliation>School of Social Sciences and Psychology, Western Sydney University, Sydney 2751, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Social Sciences and Psychology, Western Sydney University, Sydney 2751, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney 2751, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney 2751, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author></analytic><series><title level="j">Reviews in the neurosciences</title><idno type="ISSN">0334-1763</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">Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. The severity of illness is positively related to homocysteine levels, with high homocysteine levels due to the low activity of the transsulfuration pathway, which metabolizes homocysteine in synthesizing L-cysteine. Glutathione levels are low in schizophrenia, which indicates shortages of L-cysteine and low activity of the transsulfuration pathway. Hydrogen sulfide (H2S) levels are low in schizophrenia. H2S is synthesized by cystathionine β-synthase and cystathionine γ-lyase, which are the two enzymes in the transsulfuration pathway. Iron-sulfur proteins obtain sulfur from L-cysteine. The oxidative phosphorylation (OXPHOS) pathway has various iron-sulfur proteins. With low levels of L-cysteine, iron-sulfur cluster formation will be dysregulated leading to deficits in OXPHOS in schizophrenia. Molybdenum cofactor (MoCo) synthesis requires sulfur, which is obtained from L-cysteine. With low levels of MoCo synthesis, molybdenum-dependent sulfite oxidase (SUOX) will not be synthesized at appropriate levels. SUOX detoxifies sulfite from sulfur-containing amino acids. If sulfites are not detoxified, there can be sulfite toxicity. The transsulfuration pathway metabolizes selenomethionine, whereby selenium from selenomethionine can be used for selenoprotein synthesis. The low activity of the transsulfuration pathway decreases selenoprotein synthesis. Glutathione peroxidase (GPX), with various GPXs being selenoprotein, is low in schizophrenia. The dysregulations of selenoproteins would lead to oxidant stress, which would increase the methylation of genes and histones leading to epigenetic changes in TRS. An add-on treatment to mainline antipsychotics is proposed for TRS that targets the dysregulations of the transsulfuration pathway and the dysregulations of other pathways stemming from the transsulfuration pathway being dysregulated.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31714892</PMID><DateRevised><Year>2020</Year><Month>01</Month><Day>11</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0334-1763</ISSN><JournalIssue CitedMedium="Internet"><Volume>31</Volume><Issue>2</Issue><PubDate><Year>2020</Year><Month>Jan</Month><Day>28</Day></PubDate></JournalIssue><Title>Reviews in the neurosciences</Title><ISOAbbreviation>Rev Neurosci</ISOAbbreviation></Journal><ArticleTitle>Treatment-resistant schizophrenia: focus on the transsulfuration pathway.</ArticleTitle><Pagination><MedlinePgn>219-232</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1515/revneuro-2019-0057</ELocationID><ELocationID EIdType="pii" ValidYN="Y">/j/revneuro.2020.31.issue-2/revneuro-2019-0057/revneuro-2019-0057.xml</ELocationID><Abstract><AbstractText>Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. The severity of illness is positively related to homocysteine levels, with high homocysteine levels due to the low activity of the transsulfuration pathway, which metabolizes homocysteine in synthesizing L-cysteine. Glutathione levels are low in schizophrenia, which indicates shortages of L-cysteine and low activity of the transsulfuration pathway. Hydrogen sulfide (H2S) levels are low in schizophrenia. H2S is synthesized by cystathionine β-synthase and cystathionine γ-lyase, which are the two enzymes in the transsulfuration pathway. Iron-sulfur proteins obtain sulfur from L-cysteine. The oxidative phosphorylation (OXPHOS) pathway has various iron-sulfur proteins. With low levels of L-cysteine, iron-sulfur cluster formation will be dysregulated leading to deficits in OXPHOS in schizophrenia. Molybdenum cofactor (MoCo) synthesis requires sulfur, which is obtained from L-cysteine. With low levels of MoCo synthesis, molybdenum-dependent sulfite oxidase (SUOX) will not be synthesized at appropriate levels. SUOX detoxifies sulfite from sulfur-containing amino acids. If sulfites are not detoxified, there can be sulfite toxicity. The transsulfuration pathway metabolizes selenomethionine, whereby selenium from selenomethionine can be used for selenoprotein synthesis. The low activity of the transsulfuration pathway decreases selenoprotein synthesis. Glutathione peroxidase (GPX), with various GPXs being selenoprotein, is low in schizophrenia. The dysregulations of selenoproteins would lead to oxidant stress, which would increase the methylation of genes and histones leading to epigenetic changes in TRS. An add-on treatment to mainline antipsychotics is proposed for TRS that targets the dysregulations of the transsulfuration pathway and the dysregulations of other pathways stemming from the transsulfuration pathway being dysregulated.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Berry</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>School of Social Sciences and Psychology, Western Sydney University, Sydney 2751, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abohamza</LastName><ForeName>Eid</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Social Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha, Qatar.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moustafa</LastName><ForeName>Ahmed A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>School of Social Sciences and Psychology, Western Sydney University, Sydney 2751, New South Wales, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney 2751, New South Wales, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Rev Neurosci</MedlineTA><NlmUniqueID>8711016</NlmUniqueID><ISSNLinking>0334-1763</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">cystathionine β-synthase</Keyword><Keyword MajorTopicYN="N">cystathionine γ-lyase</Keyword><Keyword MajorTopicYN="N">glutathione peroxidase</Keyword><Keyword MajorTopicYN="N">homocysteine</Keyword><Keyword MajorTopicYN="N">iron-sulfur cluster</Keyword><Keyword MajorTopicYN="N">oxidative phosphorylation</Keyword><Keyword MajorTopicYN="N">sulfite oxidase</Keyword><Keyword MajorTopicYN="N">treatment-resistant schizophrenia</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>06</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>07</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31714892</ArticleId><ArticleId IdType="doi">10.1515/revneuro-2019-0057</ArticleId><ArticleId IdType="pii">/j/revneuro.ahead-of-print/revneuro-2019-0057/revneuro-2019-0057.xml</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>Qatar</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Berry, Thomas" sort="Berry, Thomas" uniqKey="Berry T" first="Thomas" last="Berry">Thomas Berry</name></noRegion><name sortKey="Moustafa, Ahmed A" sort="Moustafa, Ahmed A" uniqKey="Moustafa A" first="Ahmed A" last="Moustafa">Ahmed A. Moustafa</name><name sortKey="Moustafa, Ahmed A" sort="Moustafa, Ahmed A" uniqKey="Moustafa A" first="Ahmed A" last="Moustafa">Ahmed A. Moustafa</name></country><country name="Qatar"><noRegion><name sortKey="Abohamza, Eid" sort="Abohamza, Eid" uniqKey="Abohamza E" first="Eid" last="Abohamza">Eid Abohamza</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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