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@ARTICLE{Mazargui:138966,
      author       = {Mazargui, Honoree and Lévêque, Christian and Bartnik,
                      Dirk and Fantini, Jacques and Gouget, Tiphany and Melone,
                      Mariarosa A. B. and Funke, Susanne A. and Willbold, Dieter
                      and Perrone, Lorena},
      title        = {{A} synthetic amino acid substitution of {T}yr10 in {A}β
                      peptide sequence yields a dominant negative variant in
                      amyloidogenesis},
      journal      = {Aging cell},
      volume       = {11},
      number       = {3},
      issn         = {1474-9718},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {FZJ-2013-05008},
      pages        = {530 - 541},
      year         = {2012},
      abstract     = {Alzheimer's disease (AD) is the most common cause of
                      dementia in elderly people, and age is the major nongenetic
                      risk factor for sporadic AD. A hallmark of AD is the
                      accumulation of amyloid in the brain, which is composed
                      mainly of the amyloid beta-peptide (Aβ) in the form of
                      oligomers and fibrils. However, how aging induces Aβ
                      aggregation is not yet fully determined. Some residues in
                      the Aβ sequence seem to promote Aβ-induced toxicity in
                      association with age-dependent risk factors for AD, such as
                      (i) increased GM1 brain membrane content, (ii) altered lipid
                      domain in brain membrane, (iii) oxidative stress. However,
                      the role of Aβ sequence in promoting aggregation following
                      interaction with the plasma membrane is not yet
                      demonstrated. As Tyr10 is implicated in the induction of
                      oxidative stress and stabilization of Aβ aggregation, we
                      substituted Tyr 10 with a synthetic amino acid that
                      abolishes Aβ-induced oxidative stress and shows an
                      accelerated interaction with GM1. This variant peptide shows
                      impaired aggregation properties and increased affinity for
                      GM1. It has a dominant negative effect on amyloidogenesis in
                      vitro, in cellulo, and in isolated synaptosomes. The present
                      study shed new light in the understanding of Aβ-membrane
                      interactions in Aβ-induced neurotoxicity. It demonstrates
                      the relevance of Aβ sequence in (i) Aβ-membrane
                      interaction, underlining the role of age-dependent enhanced
                      GM1 content in promoting Aβ aggregation, (ii) Aβ
                      aggregation, and (iii) Aβ-induced oxidative stress. Our
                      results open the way for the design of peptides aimed to
                      inhibit Aβ aggregation and neurotoxicity.},
      cin          = {ICS-6},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ICS-6-20110106},
      pnm          = {452 - Structural Biology (POF2-452)},
      pid          = {G:(DE-HGF)POF2-452},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000303910100019},
      pubmed       = {pmid:22385841},
      doi          = {10.1111/j.1474-9726.2012.00814.x},
      url          = {https://juser.fz-juelich.de/record/138966},
}