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German Center for Neurodegenerative Diseases - DZNE

The DZNE studies causes and mechanisms leading to the formation of neurodegenerative diseases. The aim is, by means of close collaboration between basic, health care and clinical researchers, to rapidly translate knowledge obtained in laboratories into therapeutic applications. Neurodegenerative diseases cannot be cured in most cases, but only treated palliatively. That is why the underlying pathomechanisms shall be elucidated using a variety of state-of-the art technologies at the DZNE. Of particular importance is structural biology as many factors that are important for neurodegeneration, such as mutation and post-translational modifications, alter the three-dimensional structure of proteins. It is therefore essential to characterize the three-dimensional structure of proteins in different pathological states. Proteins to be studied include intrinsically disordered proteins, proteins in membranes and protein complexes. Due to the dynamic nature and heterogeneity of many protein structures, NMR spectroscopy is particularly suited for structural biology studies in the area of neurodegeneration. NMR spectroscopy is a nanoscale microscopy technique monitoring biomolecular conformation on length scales down to 10-11 and time scales from nanoseconds to hours and longer. We further employ complementary methods such as mass spectrometry, electron microscopy and x-ray crystallography in our studies.

 

Publications:

Wang Y, Mandelkow E Tau in physiology and pathology. Nat Rev Neurosci. 2016 Jan;17(1):5-21. doi: 10.1038/nrn.2015.1. Epub 2015 Dec 3 Pubmed

Hochgräfe K, Sydow A, Matenia D, Cadinu D, Könen S, Petrova O, Pickhardt M, Goll P, Morellini F, Mandelkow E & Mandelkow EM. Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau. Acta Neuropathol Commun. 2015 May PubMed

Kadavath H, Hofele RV, Biernat J, Kumar S, Tepper K, Urlaub H, Mandelkow E & Zweckstetter M Tau stabilizes microtubules by binding at the interface between tubulin heterodimers. Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7501-6. doi:10.1073/pnas.1504081112. Epub 2015 Jun 1. PubMed

Fonseca-Ornelas L, Eisbach SE, Paulat M, Giller K, Fernández CO, Outeiro TF, Becker S & Zweckstetter M Small molecule-mediated stabilization of vesicle-associated helical α-synuclein inhibits pathogenic misfolding and aggregation. Nat Commun. 2014 Dec 19;5:5857. PubMed

Wysoczański P, Schneider C, Xiang S, Munari F, Trowitzsch S, Wahl MC, Lührmann R, Becker S & Zweckstetter M Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex. Nat Struct Mol Biol. 2014 Oct;21(10):911-8. doi: 10.1038/nsmb.2889. Epub 2014 Sep 14. PMID:25218446 PubMed

Jaremko, L., Jaremko, M., Giller, K., Becker, S. and Zweckstetter, M. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science (2014) 343/6177, 1363-1366. PubMed

Karagoz, G.E. et al. Hsp90-Tau complex reveals molecular basis for specificity in chaperone action. Cell (2014) 156, 963-74. PubMed

Akoury, E., Pickhardt, M., Gajda, M., Biernat, J., Mandelkow, E. and Zweckstetter, M. Mechanistic basis of phenothiazine-driven inhibition of Tau aggregation. Angew Chem Int Ed Engl (2013) 52, 3511-5. PubMed

Mukrasch, M.D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., Griesinger, C., Mandelkow, E. and Zweckstetter, M. Structural polymorphism of 441-residue tau at single residue resolution. PLoS Biol (2009) 7, e34.

Drewes, G., Ebneth, A., Preuss, U., Mandelkow, E.-M., Mandelkow, E.  MARK - a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. (1997) Cell 89, 297-308. PubMed

 

 

30.08.2012

Contact

 

Prof. Dr. Markus Zweckstetter

German Center for Neurodegenerative Diseases (DZNE) 
                           & 
Max-Planck Institute for Biophysical Chemistry 
                           &
University Medical Center Göttingen

Am Fassberg 11, 
37077 Göttingen, Germany

+49 551 201-2220

www.dzne.de