Institute of Anatomy

Glial Biology in Myelin Disorders (from pathomechanisms to therapy)

Image description: Neuromuscular junction in a mouse gastrocnemic muscle showing Schwann cells (orange), the axon terminal (green), the postsynaptic muscle acetylcholine receptors (purple) and cell nuclei (blue); Images: Robert Fledrich

Neuromuscular disorders are characterized by impaired motor function. The underlying primary defects, however, can be very divers and may arise not only from malfunction of neurons or muscle cells, but also glial cells. The peripheral nerve glia, the Schwann cells, provide axons with an insulating myelin sheath that facilitates rapid propagation of electrical impulses. Schwann cells moreover support nerve fibers metabolically and, in the case of terminal Schwann cells, participate in neuromuscular transmission. So far, more than 1000 mutations in over 100 genes are known to affect Schwann cell or axon function and, hence, cause chronic progressive sensory and motor impairment. These genetically determined neuropathies are collectively referred to as Charcot-Marie-Tooth (CMT) diseases and affect 1 in 2500 humans. Unfortunately, no causal therapy is available for any type of CMT neuropathy, especially because the underlying pathological mechanisms that lead to nerve impairment remain poorly understood. With the help of transgenic techniques in mice, a battery of state of the art behavioral and electrophysiological methods, ultra resolution microscopy and next generation sequencing approaches, we aim to (1) better understand the glial biology in health in disease in order to be able to (2) unravel pathological mechanisms that may help to (3) identify therapeutic targets for neuromuscular disorders and myelin associated diseases.

Porträtfoto eines freundlich lächelenden Mannes mit schwarzem Shirt und dunkelblonden kurzen Haaren

Prof. Dr. rer. nat. Robert Fledrich

Publications

Phone: +49 341 - 97 25778
E-Mail: robert.fledrich@medizin.uni-leipzig.de
Website: fledrichLAB

Team

Mika Ammermann, MD student
Aline Backhaus, MD student
Caroline Ehbrecht, MD student
Niko Fleischer, BSc student helper
Alexander Grüner, MD student
Lukas Keilitz, MD student
Dr. rer. nat. Theresa Kungl
Christina Paul, BSc (MTA, lab manager)
Erik Schäffner, MSc (PhD student)
Nele Schröter, MD student
Vlad Schuetza, MSc (PhD student)
Nancy Schwagarus (MTA, lab manager)
Josephine Wolf, MD student

Partners

Prof. Ruth M. Stassart
Dept. Neuropathology
University Hospital Leipzig

Prof. Klaus-Armin Nave
Max Planck Institute of Experimental Medicine Göttingen

Prof. Nicolas Tricaud
INSERM Montpellier

Prof. Charbel Massaad
University Descartes Paris

Prof.i Helen Morrison
Fritz Lipman Institute Jena

Prof. Michael W. Sereda
University Medical Center and MPI-EM Göttingen

Prof. Markus Schwab
Hanover University and MPI-EM Göttingen

Prof. Rudolf Martini
Würzburg University

Prof. Philipp Scherer
University of Texas, Dallas

Prof. Gwen Childs
University of Arkansas, Little Rock

Selected publications

Fledrich R, Kungl T, Nave KA, Stassart RM, (2019) Axo-glial interdependence in peripheral nerve development. Development. Nov 12;145(21). pii: dev151704. doi: 10.1242/dev.151704. PMID: 31719044

Fledrich R*, Akkermann D*, Schütza V, Abdelaal TA, Hermes D, Schäffner E, Soto-Bernardini MC, Götze T, Klink A, Kusch K, Krueger M, Kungl T, Frydrychowicz C, Möbius W, Brück W, Mueller WC, Bechmann I, Sereda MW, Schwab MH, Nave KA, Stassart RM, (2019) NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies. Nature Communications. Apr 1;10(1):1467. doi: 10.1038/s41467-019-09385-6 PMID: 30931926

Fledrich R, Abdelaal T, Rasch L, Bansal V, Schütza V, Brügger B, Lüchtenborg C, Prukop T, Stenzel J, Rahman RU, Hermes D, Ewers D, Möbius W, Ruhwedel T, Katona I, Weis J, Klein D, Martini R, Brück W, Müller WC, Bonn S, Bechmann I, Nave KA, Stassart RM*, Sereda MW*. (2018) Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. Nature Communications. Aug 2;9(1):3025. doi: 10.1038/s41467-018-05420-0. PMID: 30072689

Fledrich R*, Stassart RM*, Klink A, Rasch LM, Prukop T, Haag L, Czesnik D, Kungl T, Abdelaal TA, Keric N, Stadelmann C, Brück W, Nave KA, Sereda MW. (2014) Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A. Nature Medicine. Sep;20(9):1055-61. doi: 10.1038/nm.3664. PMID: 25150498

Stassart RM*, Fledrich R*, Velanac V, Brinkmann BG, Schwab MH, Meijer D, Sereda MW, Nave KA. (2013) A role for Schwann cell-derived neuregulin-1 in remyelination. Nature Neuroscience. Jan;16(1):48-54. doi: 10.1038/nn.3281. PMID: 23222914

Fledrich R, Schlotter-Weigel B, Schnizer TJ, Wichert SP, Stassart RM, Meyer zu Hörste G, Klink A, Weiss BG, Haag U,Walter MC, Rautenstrauss B, Paulus W, Rossner MJ, Sereda MW. (2012) A rat model of Charcot-Marie-Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients. Brain. Jan;135(Pt 1):72-87. doi: 10.1093/brain/awr322. PMID: 22189569