Prof. Dr. Carsten Korth
Investigation of protein misassembly, misfolding or misprocessing in brain diseases, and the development of pharmacotherapies to interfer with or prevent these protein pathologies. There is a focus on neurobiology and proteinbiochemistry. Generation of (mis)assembled proteins is investigated at the levels of generation, recognition and degradation in in vivo and in vitro models.
1. Neurobiology of chronic mental diseases (CMD) schizophrenia and recurrent affective disorders: Identification and characterization of CMD-associated proteins by proteomics, biochemistry, cell biology. Characterizing sporadic CMD as protein misassembly disorders. Translational research for identifying biological markers as diagnostic tests for CMD and CMD-associated conformers as pharmacological targets (Interview of International Innovation with Carsten Korth from July 2012 on Mental illness Research).
2. Cell biology and functional regulation of protein misfolding: Generation of conformation-sensitive ligands. Development of animal models for protein conformational disorders.
3. Pharmacotherapy of protein conformational diseases.
4. Neurobiology of Aging Insoluble and aggregated protein deposits are not only hallmarks of neurodegenerative disorders but are also hallmarks of the aging brain in the form of acculumating lipofuscin and other cellular debris. Dysfunctional protein degradation in the aging post-mitotic cell is investigated by proteomic, biochemical and cell biological techniques. Cross-influences to protein conformatonal diseases are revealed.
1. Trossbach SV, Bader V, Hecher L, Pum ME, Prikulis I, Schäble S, de Souza Silva MA, Su P, Boulat B, Chwiesko C, Lohr KM, Stout KA, Weisshaupt, Masoud S, Godsave SF, Bilzer T, Steiner H, Peters PJ, Bauer A, Sauvage M, Ramsey AJ, Miller GW, Liu F, Seeman P, Brandon NJ, Huston JP, Korth C. (2016) Misassembly of non-mutant Disrupted-in-schizophrenia 1 (DISC1) protein is linked to altered dopamine homeostasis and behavioral deficits. Molecular Psychiatry, in press. PubMed
2. Müller-Schiffmann A, Herring A, Abdel-Hafiz L, Schäble S, Wedel D, Tchepkova AN, Horn AHC, Sticht H, de Souza Silva MA, Sergeeva O, Gottmann K, Huston JP, Keyvani K, Korth C. (2015) Aβ dimers in the absence of plaque pathology are sufficient to impair learning and synaptic plasticity. Brain, in press, doi 10.1093/brain/awv355. PubMed
3. Bradshaw NJ, Bader V, Prikulis I, Lüking A, Müllner S, Korth C. (2014) Aggregation of the protein TRIOBP1 and its potential relevance to schizophrenia. PloS ONE 9(10):e111196. PubMed
4. Bader V, Tomppo L, Trossbach SV, Bradshaw NJ, Prikulis I, Leliveld SR, Lin CY, Ishizuka K, Sawa A, Ramos A, Rosa I, García A, Requena JR, Hipolito M, Rai N, Nwulia E, Henning U, Ferrea S, Luckhaus C, Ekelund J, Veijola J, Järvelin MR, Hennah W, Korth C (2012) Proteomic, genomic and translational approaches identify CRMP1 for a role in schizophrenia and its underlying traits. Hum Mol Genet. 21(20):4406-18. PubMed
5. Ottis P, Bader V, Trossbach S, Kretzschmar H, Michel M, Leliveld S R, Korth C (2011) Convergence of two independent mental disease genes on the protein level: recruitment of dysbindin to cellinvasive DISC1 aggresomes. Biol. Psychiatry 70:604-10. PubMed
6. Müller-Schiffmann A, März J, Andreyeva A, Rönicke R, Bartnik D, Brener O, Kutzsche J, Horn A H C, Gottmann K, Reymann K, Funke S A, Nagel-Steger L, Moriscot C, Schoehn G, Sticht H, Willbold D, Schrader T, Korth C (2010). Combining independent drug classes into superior, synergistically acting hybrid molecules. Angew. Chem. Int. Ed. 49:8743-46. PubMed
7. Seshadri S, Kamiya A, Yokota Y, Prikulis I, Kano S I, Hayashi-Takagi A, Stanco A, Rao S, Ishikuza K, Wong P, Korth C, Anton E S, Sawa A (2010). Disrupted-in-Schizophrenia-1 expression is regulated by BACE1-Neuregulin cascade. Proc. Natl. Acad. Sci. USA 107:5622-5627. PubMed
8. Leliveld S R, Bader V, Hendriks P, Prikulis I, Sajnani G, Requena J, Korth C (2008). Insolubility of DISC1 disrupts oligomer-dependent interactions with NDEL1 and is associated with sporadic mental disease. J. Neurosci. 28:3839-3845. PubMed
9. Korth C, May B, Cohen F, Prusiner S B (2001). Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc. Natl. Acad. Sci. USA 98:9836-9841. PubMed
10. Korth C, Stierli B, Streit P, Moser M, Schaller O, Fischer R, Schulz-Schaeffer W, Kretzschmar H, Raeber A, Braun U, Ehrensperger F, Hornemann S, Glockshuber R, Riek R, Billeter M, Wuthrich K, Oesch B (1997). Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390:74-77. PubMed