Graduate School of Systemic Neurosciences GSN-LMU
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Dieter Edbauer

Prof. Dr. Dieter Edbauer

GSN associate faculty

Responsibilities

Research group leader "Cell Biology of Neurodegeneration"

Contact

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Feodor-Lynen-Str. 17
D-81377 Munich

Phone: +49 (0)89 / 4400-46510
Fax: +49 (0)89 / 4400-46508

Website: http://www.biochemie.abi.med.uni-muenchen.de/about/staff/scientists/edbauer/index.html
Website: http://www.dzne.de/en/sites/munich/research-groups/edbauer.html

Further Information

Research focus:

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases with overlapping genetics and pathology. The most common cause is expansion of a GGGGCC repeat in the first intron of the gene C9orf72. We discovered that the repeat region is translated in all reading frames into aggregating dipeptide-repeat (DPR) proteins despite its intronic localization and lack of an ATG start codon (Mori&Weng et al., Science 2013). DPR aggregates outnumber the previously identified TDP-43 inclusions in the hippocampus, cortex and cerebellum. Some patients exclusively show DPR pathology, strongly suggesting DPR production is a key pathomechanism in C9orf72 mutation carriers. However, we know next to nothing about the mechanisms of translation, toxicity, aggregation and clearance of DPR proteins. In an ERC funded project, we now characterize this unusual pathomechanism in detail using diverse model systems combined with in depth analysis of the pathology in patient tissue. Using these models we will develop strategies to inhibit expression, aggregation and toxicity of DPR proteins. We also have a strong interest in pathomechanisms in other forms of FTD/ALS and Alzheimer’s disease. We apply cutting edge methods ranging from lentiviral manipulation of primary neuron cultures, live imaging, proteomic approaches, CRISPR/Cas9 genome editing to human pathology and next generation sequencing.

Key words: Mechanisms of neurodegeneration, therapeutic approaches, cell biology of neurons, biochemistry, RNA biology, live imaging, intracellular trafficking, human pathology

Current GSN students: Bahram Khosravi

Selected publications:

Schwenk BM, Hartmann H, Serdaroglu A, Schludi MH, Hornburg D, Meissner F, Orozco D, Colombo A, Tahirovic S, Michaelsen M, Schreiber F, Haupt S, Peitz M, Brüstle O, Küpper C, Klopstock T, Otto M, Ludolph AC, Arzberger T, Kuhn PH, Edbauer D. (2016) TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons. EMBO J. 35(21): 2350-2370

Edbauer D, Haass C. (2016) An amyloid-like cascade hypothesis for C9orf72 ALS/FTD. Curr Opin Neurobiol. 36:99-106

Schludi MH, May S, Grässer FA, Rentzsch K, Kremmer E, Küpper C, Klopstock T; German Consortium for Frontotemporal Lobar Degeneration; Bavarian Brain Banking Alliance, Arzberger T, Edbauer D. (2015) Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing. Acta Neuropathol. 130(4):537-55

May S, Hornburg D, Schludi MH, Arzberger T, Rentzsch K, Schwenk BM, Grässer FA, Mori K, Kremmer E, Banzhaf-Strathmann J, Mann M, Meissner F, Edbauer D. (2014) C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta Neuropathol. 128:485-503.

Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, Fischer A, Edbauer D. (2014) MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease. EMBO J. 33:1667-80.