Team TNA: Tau-mediated neurodegeneration in Alzheimer’s disease
Alzheimer’s disease is the most common form of dementia worldwide, affecting millions of patients, with no therapeutic options available to date. While amyloid plaques have long been recognized as hallmarks of the disease, recent evidence suggests that abnormal post-translational modifications of the Tau protein are strongly involved in disease manifestation and progression. In Alzheimer’s disease, Tau is unable to perform its normal function in the stabilization of microtubules and is prone to hyperphosphorylation, aggregation and secretion.
We study the network of Tau post-translational modifications, interactions between different types of modifications, and their impact on Tau function and dysfunction in the disease state using materials obtained from sporadic Alzheimer’s disease patients as well as neurons derived from induced pluripotent stem cells. Analytical and biochemical approaches and screening methods are used to identify tractable therapeutic targets in Tau post-translational modification pathways that can serve as starting points for the development of therapeutic agents. We aim to define a characteristic signature of pathologic Tau post-translational modifications that will serve as a biomarker to support the diagnosis and monitor the progression of Alzheimer’s disease.
- Ercan E, Eid S, Weber C, Kowalski A, Bichmann M, Behrendt A, Matthes F, Krauss S, Reinhardt P, Fulle S, Ehrnhoefer DE.
A validated antibody panel for the characterization of tau post-translational modifications.
Molecular Neurodegeneration. 2017
- Schöndorf DC, Elschami M, Schieck M, Ercan-Herbst E, Weber C, Riesinger Y, Kalman S, Steinemann D, Ehrnhoefer DE.
Generation of an induced pluripotent stem cell cohort suitable to investigate sporadic Alzheimer’s Disease.
Stem Cell Res. 2018
- Behrendt A, Bichmann M, Ercan-Herbst E, Haberkant P, Schöndorf DC, Wolf M, Fahim SA, Murolo E, Ehrnhoefer DE.
Asparagine endopeptidase cleaves tau at N167 after uptake into microglia.
Neurobiol Dis. 2019
- Ercan-Herbst E, Ehrig J, Schöndorf DC, Behrendt A, Klaus B, Gomez Ramos B, Prat Oriol N, Weber C, Ehrnhoefer DE.
A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer’s disease brain.
Acta Neuropathol Commun. 2019