Areas of investigation/research focus

Joint outline with Eckhard 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

Dennissen FJ, Anglada-Huguet M, Sydow A, Mandelkow E, Mandelkow E-M. Adenosine A1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280. Proc Natl Acad Sci USA. 2016 Jan 01; 113:11597-11602. doi: 10.1073/pnas.1603119113
Hans Zempel, Julia Luedtke, Yatender Kumar, Jacek Biernat, Hana Dawson, Eckhard Mandelkow, Eva-Maria Mandelkow. Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. EMBO Journal. 2013 Nov 12; 32:2920-2937. doi: 10.1038/emboj.2013.207
Braak E, Braak H, Mandelkow E-M. A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol. 1994 Jan 01; 87:554-67.
Mandelkow E-M, Mandelkow E, Milligan RA. Microtubule dynamics and microtubule caps: A time-resolved cryo-electron microscopy study. J Cell Biol. 1991 Jan 01; 114:977-91.
Mandelkow E-M, Harmsen A, Mandelkow E, Bordas J. X-ray kinetic studies of microtubule assembly using synchrotron radiation. Nature. 1980 Jan 01; 287:595-9.

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