Structural Principles of Neurodegeneration
Prof. Dr. Eckhard Mandelkow
Group Leader
Ludwig-Erhard-Allee 2
53175 Bonn

eckhard.mandelkow@dzne.de
 +49 228 43302-630

Areas of investigation/research focus

Joint outline with Eva-Maria Mandelkow

Neuronal cytoskeleton and Alzheimer disease

The two groups use complementary approaches to investigate the structure and function of the neuronal cytoskeleton, the neurofibrillary pathology of Alzheimer disease, and to develop therapeutic strategies.

The research includes biophysical methods to investigate protein structures and their aggregation pathways 
(e.g. electron microscopy, X-ray scattering, spectroscopic methods), biochemical methods (protein interactions, enzyme activities), cell biological methods (development of cellular models of disease states, analysis of transport and aggregation mechanisms by imaging methods) and animal models of neurodegeneration (e.g. transgenic mouse models of Tau-induced pathology).

Examples are:

  • microtubule assembly, interactions with associated proteins (MAPs) and motor proteins
  • Tau protein and pathological changes in Alzheimer disease and other "tauopathies"
  • Functional studies of protein kinases regulating the tau-microtubule interactions
  • Axonal transport mechanisms by motor proteins
  • Neuronal cell models of Alzheimer disease
  • Animal models of Alzheimer disease (transgenic mice, C. elegans)
  • Development of Tau aggregation inhibitors and modulators of Tau toxicity for therapy

"Morris Water Maze" swim test to probe memory

  • Mice are trained to find and remember a platform (white circle).
  • Short path = good memory (left and right),
  • long path = poor memory (middle). 

Kinwalk and KTdock

 

 

Key Publications

Xiaoyu Li, Yatender Kumar, Hans Zempel, Eva-Maria Mandelkow, Jacek Biernat, Eckhard Mandelkow. Novel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration. EMBO Journal. 2011 Nov. 29; 30:4825-4837. doi: 10.1038/emboj.2011.376
von Bergen M, Friedhoff P, Biernat J, Heberle J, Mandelkow E-M, Mandelkow E. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif (306-VQIVYK-311) forming beta structure. Proc Natl Acad Sci USA. 2000 Jan. 01; 97:5129-34. doi: 10.1073/pnas.97.10.5129
Kozielski F, Sack S, Marx A, Thormählen M, ..., Mandelkow E-M, Mandelkow E. The crystal structure of dimeric kinesin and implications for microtubule-dependent motility. Cell. 1997 Jan. 01; 91:985-94. doi: 10.1016/S0092-8674(00)80489-4
Mandelkow E, Mandelkow E-M, Hotani H, Hess B, Müller SC. Spatial patterns from oscillating microtubules. Science. 1989 Jan. 01; 246:1291-3.
Wille H, Drewes G, Biernat J, Mandelkow E-M, Mandelkow E. Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J Cell Biol. 1992 Jan. 01; 118:573-84.

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