162830 20230915092409.0 10.3389/fgene.2021.761714 doi pmid:34659371 pmid pmc:PMC8517220 pmc altmetric:114312454 altmetric DZNE-2021-01485 English 570 Heinz, Annika 0 The MID1 Protein: A Promising Therapeutic Target in Huntington's Disease. Lausanne 2021 Frontiers Media article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1655472191_22304 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote (CC BY) Huntington'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. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Alzheimer’s disease Other CAG repeat Other Huntington’s disease Other MID1 Other RNA-protein interaction Other RNA-targeting drug Other mRNA translation Other Schilling, Judith P:(DE-2719)2810643 1 van Roon-Mom, Willeke 2 Krauß, Sybille P:(DE-HGF)0 3 10.3389/fgene.2021.761714 Vol. 12, p. 761714 PERI:(DE-600)2606823-0 761714 Frontiers in genetics 12 2021 1664-8021 OpenAccess http://pub.dzne.de/record/162830/files/DZNE-2021-01485.pdf OpenAccess pdfa http://pub.dzne.de/record/162830/files/DZNE-2021-01485.pdf?subformat=pdfa oai:pub.dzne.de:162830 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810643 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 2021 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-05-04 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-05-04 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-05-04 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-05-04 Fees StatID:(DE-HGF)0700 StatID 2021-05-04 OpenAccess StatID:(DE-HGF)0510 StatID Article Processing Charges StatID:(DE-HGF)0561 StatID 2021-05-04 JCR StatID:(DE-HGF)0100 StatID FRONT GENET : 2021 2022-11-08 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-08 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-08 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-05-04T10:15:44Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-05-04T10:15:44Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-05-04T10:15:44Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-08 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-08 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-08 IF < 5 StatID:(DE-HGF)9900 StatID 2022-11-08 I:(DE-2719)1011006 AG Krauß Regulatory RNA-protein interaction in neurodegenerative diseases 0 journal VDB UNRESTRICTED I:(DE-2719)1011006 FullTexts