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Ottis P, Bader V, Trossbach SV, Kretzschmar H, Michel M, Leliveld SR, Korth C. Convergence of two independent mental disease genes on the protein level: recruitment of dysbindin to cell-invasive disrupted-in-schizophrenia 1 aggresomes. Biol Psychiatry . 2011 Oct 1 ; 70(7):604-10. PubMed Abstract

Comments on Paper and Primary News
Comment by:  T.A. AtkinJosef Kittler
Submitted 13 June 2011 Posted 13 June 2011

Protein aggregation is a well-characterized disease mechanism in multiple neurodegenerative disorders. Formation of Lewy bodies is a hallmark feature of Parkinson’s disease; tau and amyloid-β aggregation precedes symptoms in Alzheimer’s disease; and mutant huntingtin aggregation occurs in Huntington’s disease (Ross and Poirier, 2004). Interestingly, protein aggregation has recently emerged as a disease mechanism in schizophrenia (Leliveld et al., 2008; Leliveld et al., 2009; Atkin TA, 2009; Zhou et al., 2010), but the function of these protein aggregates remains unknown. In a recent paper by Ottis et al., a new pathological feature of DISC1 aggregates has been revealed, in addition to a novel binding partner. First the authors find that DISC1 aggregates are cell invasive, suggesting a new pathological feature of these interesting structures. Secondly, they find that DISC1 aggregates can...  Read more

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Comment by:  Carsten Korth, SRF Advisor
Submitted 14 June 2011 Posted 14 June 2011

These are valuable comments, and I would agree in seeing our report as the beginning rather than the end of a story. I would like to specifically comment on the cell-invasiveness of DISC1 aggresomes.

Cell invasiveness of protein aggregates may be less rare than initially thought. In the last two years, this has been established for a range of proteins associated with protein conformational diseases. The initial paper on seeded nucleation of Aβ (Meyer-Luehmann et al., 2006) was recently joined by papers demonstrating invasiveness of cytosolic proteins α-synuclein (Desplats et al., 2009), polyglutamine protein (Ren et al., 2009), tau (Clavaguera et al., 2009), and SOD1 aggregates (Münch et al., 2011), making cell-invasiveness a hallmark for progressive brain diseases like the presence of misfolded proteins in these diseases itself. A...  Read more

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