% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Aillaud:163637,
      author       = {Aillaud, Isabelle and Kaniyappan, Senthilvelrajan and
                      Chandupatla, Ram Reddy and Ramirez, Lisa-Marie and
                      Alkhashrom, Sewar and Eichler, Jutta and Horn, Anselm H C
                      and Zweckstetter, Markus and Mandelkow, Eckhard and Sticht,
                      Heinrich and Funke, Susanne Aileen},
      title        = {{A} novel {D}-amino acid peptide with therapeutic potential
                      ({ISAD}1) inhibits aggregation of neurotoxic
                      disease-relevant mutant {T}au and prevents {T}au toxicity in
                      vitro.},
      journal      = {Alzheimer's research $\&$ therapy},
      volume       = {14},
      number       = {1},
      issn         = {1758-9193},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2022-00383},
      pages        = {15},
      year         = {2022},
      abstract     = {Alzheimer's disease (AD), the most common form of dementia,
                      is a progressive neurodegenerative disorder that mainly
                      affects older adults. One of the pathological hallmarks of
                      AD is abnormally aggregated Tau protein that forms fibrillar
                      deposits in the brain. In AD, Tau pathology correlates
                      strongly with clinical symptoms, cognitive dysfunction, and
                      neuronal death.We aimed to develop novel therapeutic D-amino
                      acid peptides as Tau fibrillization inhibitors. It has been
                      previously demonstrated that D-amino acid peptides are
                      protease stable and less immunogenic than L-peptides, and
                      these characteristics may render them suitable for in vivo
                      applications. Using a phage display procedure against wild
                      type full-length Tau (TauFL), we selected a novel Tau
                      binding L-peptide and synthesized its D-amino acid version
                      ISAD1 and its retro inversed form, ISAD1rev,
                      respectively.While ISAD1rev inhibited Tau aggregation only
                      moderately, ISAD1 bound to Tau in the aggregation-prone PHF6
                      region and inhibited fibrillization of TauFL,
                      disease-associated mutant full-length Tau (TauFLΔK,
                      TauFL-A152T, TauFL-P301L), and pro-aggregant repeat domain
                      Tau mutant (TauRDΔK). ISAD1 and ISAD1rev induced the
                      formation of large high molecular weight TauFL and TauRDΔK
                      oligomers that lack proper Thioflavin-positive β-sheet
                      conformation even at lower concentrations. In silico
                      modeling of ISAD1 Tau interaction at the PHF6 site revealed
                      a binding mode similar to those known for other PHF6 binding
                      peptides. Cell culture experiments demonstrated that ISAD1
                      and its inverse form are taken up by N2a-TauRDΔK cells
                      efficiently and prevent cytotoxicity of externally added Tau
                      fibrils as well as of internally expressed TauRDΔK.ISAD1
                      and related peptides may be suitable for therapy development
                      of AD by promoting off-pathway assembly of Tau, thus
                      preventing its toxicity.},
      keywords     = {Aged / Alzheimer Disease: drug therapy / Alzheimer Disease:
                      pathology / Amino Acids: therapeutic use / Cells, Cultured /
                      Humans / Peptides: therapeutic use / Protein Conformation,
                      beta-Strand / tau Proteins: metabolism / tau Proteins:
                      toxicity / Alzheimer’s disease (Other) / D-amino
                      acid peptides (Other) / Phage display (Other) / Tau
                      aggregation inhibitors (Other) / Therapy (Other) / Amino
                      Acids (NLM Chemicals) / Peptides (NLM Chemicals) / tau
                      Proteins (NLM Chemicals)},
      cin          = {AG Mandelkow 2 / AG Mandelkow 1 / AG Zweckstetter},
      ddc          = {610},
      cid          = {I:(DE-2719)1013015 / I:(DE-2719)1013014 /
                      I:(DE-2719)1410001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35063014},
      pmc          = {pmc:PMC8783508},
      doi          = {10.1186/s13195-022-00959-z},
      url          = {https://pub.dzne.de/record/163637},
}