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@ARTICLE{Matthes:140621,
      author       = {Matthes, Frank and Hettich, Moritz M and Schilling, Judith
                      and Flores-Dominguez, Diana and Blank, Nelli and Wiglenda,
                      Thomas and Buntru, Alexander and Wolf, Hanna and Weber,
                      Stephanie and Vorberg, Ina and Dagane, Alina and Dittmar,
                      Gunnar and Wanker, Erich and Ehninger, Dan and Krauß,
                      Sybille},
      title        = {{I}nhibition of the {MID}1 protein complex: a novel
                      approach targeting {APP} protein synthesis.},
      journal      = {Cell death discovery},
      volume       = {4},
      number       = {1},
      issn         = {2058-7716},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2020-06943},
      pages        = {4},
      year         = {2018},
      abstract     = {Alzheimer's disease (AD) is characterized by two
                      neuropathological hallmarks: senile plaques, which are
                      composed of amyloid-β (Aβ) peptides, and neurofibrillary
                      tangles, which are composed of hyperphosphorylated tau
                      protein. Aβ peptides are derived from sequential
                      proteolytic cleavage of the amyloid precursor protein (APP).
                      In this study, we identified a so far unknown mode of
                      regulation of APP protein synthesis involving the MID1
                      protein complex: MID1 binds to and regulates the translation
                      of APP mRNA. The underlying mode of action of MID1 involves
                      the mTOR pathway. Thus, inhibition of the MID1 complex
                      reduces the APP protein level in cultures of primary
                      neurons. Based on this, we used one compound that we
                      discovered previously to interfere with the MID1 complex,
                      metformin, for in vivo experiments. Indeed, long-term
                      treatment with metformin decreased APP protein expression
                      levels and consequently Aβ in an AD mouse model.
                      Importantly, we have initiated the metformin treatment late
                      in life, at a time-point where mice were in an already
                      progressed state of the disease, and could observe an
                      improved behavioral phenotype. These findings together with
                      our previous observation, showing that inhibition of the
                      MID1 complex by metformin also decreases tau
                      phosphorylation, make the MID1 complex a particularly
                      interesting drug target for treating AD.},
      cin          = {AG Krauß / AG Ehninger / AG Vorberg},
      ddc          = {610},
      cid          = {I:(DE-2719)1011006 / I:(DE-2719)1013005 /
                      I:(DE-2719)1013004},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29531801},
      pmc          = {pmc:PMC5841321},
      doi          = {10.1038/s41420-017-0003-8},
      url          = {https://pub.dzne.de/record/140621},
}