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@ARTICLE{Elfgen:862746,
      author       = {Elfgen, Anne and Hupert, Michelle and Bochinsky, Kevin and
                      Tusche, Markus and González de San Román Martin, Estibaliz
                      and Gering, Ian and Sacchi, Silvia and Pollegioni, Loredano
                      and Huesgen, Pitter F. and Hartmann, Rudolf and
                      Santiago-Schübel, Beatrix and Kutzsche, Janine and
                      Willbold, Dieter},
      title        = {{M}etabolic resistance of the {D}-peptide {RD}2 developed
                      for direct elimination of amyloid-β oligomers},
      journal      = {Scientific reports},
      volume       = {9},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2019-02988},
      pages        = {5715},
      year         = {2019},
      abstract     = {Alzheimer’s disease (AD) is a neurodegenerative disorder
                      leading to dementia. Aggregation of the amyloid-β peptide
                      (Aβ) plays an important role in the disease, with Aβ
                      oligomers representing the most toxic species. Previously,
                      we have developed the Aβ oligomer eliminating therapeutic
                      compound RD2 consisting solely of D-enantiomeric amino acid
                      residues. RD2 has been described to have an oral
                      bioavailability of more than $75\%$ and to improve cognition
                      in transgenic Alzheimer’s disease mouse models after oral
                      administration. In the present study, we further examined
                      the stability of RD2 in simulated gastrointestinal fluids,
                      blood plasma and liver microsomes. In addition, we have
                      examined whether RD2 is a substrate for the human D-amino
                      acid oxidase (hDAAO). Furthermore, metabolite profiles of
                      RD2 incubated in human, rodent and non-rodent liver
                      microsomes were compared across species to search for
                      human-specific metabolites that might possibly constitute a
                      threat when applying the compound in humans. RD2 was
                      remarkably resistant against metabolization in all
                      investigated media and not converted by hDAAO. Moreover, RD2
                      did not influence the activity of any of the tested enzymes.
                      In conclusion, the high stability and the absence of
                      relevant human-specific metabolites support RD2 to be safe
                      for oral administration in humans.},
      cin          = {ICS-6 / ZEA-3},
      ddc          = {600},
      cid          = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)ZEA-3-20090406},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30952881},
      UT           = {WOS:000463482800054},
      doi          = {10.1038/s41598-019-41993-6},
      url          = {https://juser.fz-juelich.de/record/862746},
}