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@ARTICLE{Heinz:162830,
      author       = {Heinz, Annika and Schilling, Judith and van Roon-Mom,
                      Willeke and Krauß, Sybille},
      title        = {{T}he {MID}1 {P}rotein: {A} {P}romising {T}herapeutic
                      {T}arget in {H}untington's {D}isease.},
      journal      = {Frontiers in genetics},
      volume       = {12},
      issn         = {1664-8021},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DZNE-2021-01485},
      pages        = {761714},
      year         = {2021},
      note         = {(CC BY)},
      abstract     = {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.},
      keywords     = {Alzheimer’s disease (Other) / CAG repeat (Other) /
                      Huntington’s disease (Other) / MID1 (Other) / RNA-protein
                      interaction (Other) / RNA-targeting drug (Other) / mRNA
                      translation (Other)},
      cin          = {AG Krauß},
      ddc          = {570},
      cid          = {I:(DE-2719)1011006},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34659371},
      pmc          = {pmc:PMC8517220},
      doi          = {10.3389/fgene.2021.761714},
      url          = {https://pub.dzne.de/record/162830},
}