Citation link: http://dx.doi.org/10.25819/ubsi/10127
DC FieldValueLanguage
dc.contributor.authorHeinz, Annika-
dc.contributor.authorKrauß, Sybille-
dc.contributor.authorSchilling, Judith-
dc.contributor.authorvan Roon-Mom, Willeke-
dc.date.accessioned2022-06-23T10:42:36Z-
dc.date.available2022-06-23T10:42:36Z-
dc.date.issued2021de
dc.descriptionFinanziert aus dem Open-Access-Publikationsfonds der Universität Siegen für Zeitschriftenartikelde
dc.description.abstractHuntington’s disease (HD) is caused by an expansion mutation of a CAG repeat in exon 1 of the huntingtin (HTT) gene, that encodes an expanded polyglutamine tract in the HTT protein. HD is characterized by progressive psychiatric and cognitive symptoms associated with a progressive movement disorder. HTT is ubiquitously expressed, but the pathological changes caused by the mutation are most prominent in the central nervous system. Since the mutation was discovered, research has mainly focused on the mutant HTT protein. But what if the polyglutamine protein is not the only cause of the neurotoxicity? Recent studies show that the mutant RNA transcript is also involved in cellular dysfunction. Here we discuss the abnormal interaction of the mutant HTT transcript with a protein complex containing the MID1 protein. MID1 aberrantly binds to CAG repeats and this binding increases with CAG repeat length. Since MID1 is a translation regulator, association of the MID1 complex stimulates translation of mutant HTT mRNA, resulting in an overproduction of polyglutamine protein. Thus, blocking the interaction between MID1 and mutant HTT mRNA is a promising therapeutic approach. Additionally, we show that MID1 expression in the brain of both HD patients and HD mice is aberrantly increased. This finding further supports the concept of blocking the interaction between MID1 and mutant HTT mRNA to counteract mutant HTT translation as a valuable therapeutic strategy. In line, recent studies in which either compounds affecting the assembly of the MID1 complex or molecules targeting HTT RNA, show promising results.en
dc.identifier.doihttp://dx.doi.org/10.25819/ubsi/10127-
dc.identifier.urihttps://dspace.ub.uni-siegen.de/handle/ubsi/2216-
dc.identifier.urnurn:nbn:de:hbz:467-22160-
dc.language.isoende
dc.sourceFrontiers in Genetics ; 2021. - https://doi.org/10.3389/fgene.2021.761714de
dc.subject.ddc570 Biowissenschaften; Biologiede
dc.subject.otherMID1en
dc.subject.otherRNA-protein interactionen
dc.subject.otherCAG repeaten
dc.subject.otherRNA-targeting drugen
dc.subject.swbHuntington-Choreade
dc.subject.swbAlzheimerkrankheitde
dc.subject.swbTranslation <Genetik>de
dc.subject.swbMessenger-RNSde
dc.titleThe MID1 protein: a promising therapeutic target in Huntington’s diseaseen
dc.typeArticlede
item.fulltextWith Fulltext-
ubsi.publication.affiliationInstitut für Biologiede
ubsi.source.doi10.3389/fgene.2021.761714-
ubsi.source.issn1664-8021-
ubsi.source.issued2021de
ubsi.source.issuenumber12de
ubsi.source.pages7de
ubsi.source.placeLausannede
ubsi.source.publisherFrontiers Mediade
ubsi.source.titleFrontiers in Geneticsde
ubsi.subject.ghbsVOHde
ubsi.subject.ghbsVVGde
ubsi.subject.ghbsVYCde
Appears in Collections:Publikationen aus der Universität Siegen
Files in This Item:
File Description SizeFormat
The_MID1_protein.pdf1.45 MBAdobe PDFThumbnail
View/Open

This item is protected by original copyright

Show simple item record

Page view(s)

12
checked on Jun 25, 2022

Download(s)

3
checked on Jun 25, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.