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@ARTICLE{VillarPiqu:820731,
      author       = {Villar-Piqué, Anna and Lopes da Fonseca, Tomás and
                      Sant’Anna, Ricardo and Szegö, Éva Mónika and
                      Fonseca-Ornelas, Luis and Pinho, Raquel and Carija, Anita
                      and Gerhardt, Ellen and Masaracchia, Caterina and Abad
                      Gonzalez, Enrique and Rossetti, Giulia and Carloni, Paolo
                      and Fernández, Claudio O. and Foguel, Debora and Milosevic,
                      Ira and Zweckstetter, Markus and Ventura, Salvador and
                      Outeiro, Tiago Fleming},
      title        = {{E}nvironmental and genetic factors support the
                      dissociation between α-synuclein aggregation and toxicity},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {113},
      number       = {42},
      issn         = {1091-6490},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {FZJ-2016-05999},
      pages        = {E6506 - E6515},
      year         = {2016},
      abstract     = {Synucleinopathies are a group of progressive disorders
                      characterized by the abnormal aggregation and accumulation
                      of α-synuclein (aSyn), an abundant neuronal protein that
                      can adopt different conformations and biological properties.
                      Recently, aSyn pathology was shown to spread between neurons
                      in a prion-like manner. Proteins like aSyn that exhibit
                      self-propagating capacity appear to be able to adopt
                      different stable conformational states, known as protein
                      strains, which can be modulated both by environmental and by
                      protein-intrinsic factors. Here, we analyzed these factors
                      and found that the unique combination of the
                      neurodegeneration-related metal copper and the pathological
                      H50Q aSyn mutation induces a significant alteration in the
                      aggregation properties of aSyn. We compared the aggregation
                      of WT and H50Q aSyn with and without copper, and assessed
                      the effects of the resultant protein species when applied to
                      primary neuronal cultures. The presence of copper induces
                      the formation of structurally different and less-damaging
                      aSyn aggregates. Interestingly, these aggregates exhibit a
                      stronger capacity to induce aSyn inclusion formation in
                      recipient cells, which demonstrates that the structural
                      features of aSyn species determine their effect in neuronal
                      cells and supports a lack of correlation between toxicity
                      and inclusion formation. In total, our study provides strong
                      support in favor of the hypothesis that protein aggregation
                      is not a primary cause of cytotoxicity.},
      cin          = {IAS-5 / INM-9 / GRS Jülich ; German Research School for
                      Simulation Sciences / JSC},
      ddc          = {000},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121 /
                      I:(DE-Juel1)GRS-20100316 / I:(DE-Juel1)JSC-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572) / 511 -
                      Computational Science and Mathematical Methods (POF3-511)},
      pid          = {G:(DE-HGF)POF3-572 / G:(DE-HGF)POF3-511},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000385610400024},
      pubmed       = {pmid:27708160},
      doi          = {10.1073/pnas.1606791113},
      url          = {https://juser.fz-juelich.de/record/820731},
}