Prof. Dr. Stefan Lichtenthaler

Brief research description: We study how Alzheimer’s disease develops in the brain on the molecular and cellular level. The aim of our research is to better understand the disease causes and to develop new diagnostic, therapeutic and preventive approaches. Additionally, we want to predict possible side effects of Alzheimer-targeted drugs and, thus, make drug development safer. For our interdisciplinary research we use a variety of modern methods from biochemistry, proteomics, molecular, cellular and neurobiology as well as in vitro and in vivo models of Alzheimer’s disease. The focus of our research is on the molecular scissors (proteases) ADAM10 (alpha-secretase), BACE1 (beta-secretase) und gamma-secretase as well as microglia-dependent inflammatory processes in the brain. These molecules and processes have a central role in Alzheimer’s pathogenesis. We investigate their physiological function in the healthy brains and develop ways to specifically target them for a treatment of Alzheimer’s disease.

Key words: Alzheimer's disease, secretases, neuroinflammation, microglia, proteomics

• Current GSN students: Andree Schmidt, Laura Hoffmann
• Graduated GSN students: Dr. Martina Pigoni
  

Selected publications:

Güner G, Aßfalg M, Zhao K, Dreyer T, Lahiri S, Lo Y, Slivinschi BI, Imhof A, Jocher G, Strohm L, Behrends C, Langosch D, Bronger H, Nimsky C, Bartsch JW, Riddell SR, Steiner H, Lichtenthaler SF (2022). Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for µ-secretase activity. EMBO Mol Med, 14: e16084.

Jocher G, Grass V, Tschirner SK, Riepler L, Breimann S, Kaya T, Oelsner M, Hamad MS, Hofmann LI, Blobel CP, Schmidt-Weber CB, Gokce O, Jakwerth CA, Trimpert J, Kimpel J, Pichlmair A, Lichtenthaler SF (2022). ADAM10 and ADAM17 promote SARS-COV-2 cell entry and spike protein-mediated lung cell fusion. EMBO Rep, 23: e54305.

McDade E, Voytyuk I, Aisen P, Bateman R, Carrillo M, DeStrooper B, Haass C, Reiman E, Sperling R, Tariot P, Yan R, Masters C, Vassar R, Lichtenthaler SF (2021). The case for low-level BACE1 inhibition for the prevention of Alzheimer’s disease. Nature Rev Neurol, 17: 703-714.

Tüshaus J, Müller SA, Kataka ES, Zaucha J, Sebastian Monasor L, Su M, Güner G, Jocher G, Tahirovic S, Frishman D, Simons M, Lichtenthaler SF (2020). An optimized quantitative proteomics method establishes the cell type-resolved mouse brain secretome. EMBO J, 39, e105693.

Pigoni M, Hsia HE, Hartmann J, Rudan Njavro J, Shmueli MD, Müller SA, Güner G, Tüshaus J, Kuhn PH, Kumar R, Gao P, Tran ML, Ramazanov B, Blank B, Hipgrave Ederveen AL, Von Blume J, Mulle C, Gunnersen JM, Wuhrer M, Rammes G, Busche MA, Koeglsperger T, Lichtenthaler SF (2020). Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3. EMBO J, 39, e103457.

Lichtenthaler SF, Güner G (2019). Pathology-linked protease caught in action. Science, 363, 690-691.