Pathogenesis of inherited neuropathies: implication of components of the innate and adaptive immune system

• Applicant: Professor Dr. Rudolf Martini
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2013 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 227548520

• Final Report Year: 2020

Final Report Abstract

In summary, we can support our leading hypothesis that Schwann cell borne PDGF-A (and/or PDGF-B) might function as the initially unknown “activator 1” for inducing CSF-1 in peripheral nerves of CMT1 models. Conditional inactivation of PDGF-A specifically in Schwann cells led to a reduced expression of CSF-1, accompanied by a reduction of pathogenic macrophages and improved axonal preservation in Cx32def mice. It will be exciting also to decipher the role of the PDGF-B isoform in this context, as our corresponding in vitro experiments would predict a similar function.

Publications

• 2018. Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration. EMBO J. 37
  Shashi, V., M.M. Magiera, D. Klein, .... R. Martini, C. Janke, and J. Senderek
  (See online at https://doi.org/10.15252/embj.2018100540)
• 2018. Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice. The Journal of Neuroscience 38:4610-4620
  Yuan, X., D. Klein, S. Kerscher, B.L. West, J. Weis, I. Katona, and R. Martini
  (See online at https://doi.org/10.1523/JNEUROSCI.3030-17.2018)
• 2018. Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. Nat Commun. 9:3025
  Fledrich, R., T. Abdelaal, L. Rasch, V. Bansal, V. Schutza, B. Brugger, C. Luchtenborg, T. Prukop, J. Stenzel, R.U. Rahman, D. Hermes, D. Ewers, W. Mobius, T. Ruhwedel, I. Katona, J. Weis, D. Klein, R. Martini, W. Bruck, W.C. Muller, S. Bonn, I. Bechmann, K.A. Nave, R.M. Stassart, and M.W. Sereda
  (See online at https://doi.org/10.1038/s41467-018-05420-0)
• 2018. Translational Science of Rare Diseases – From Rare to Care III, Tutzing, Germany: “Early onset targeting of macrophages ameliorates neuropathic changes in a mouse model for Charcot-Marie-Tooth 1A disease”
  D. Klein, J. Groh, X. Yuan, B.L. West, and R. Martini
  
• 2019. Current Topics in Myelin Research, Kassel, Germany: “Physical Exercise as a possible Therapy for CMT1X”
  D. Klein, X. Yuan, J. Groh, and R. Martini
  
• 2019. Targeting microglia attenuates neuroinflammation-related neural damage in mice carrying human PLP1 mutations. Glia. 67:277-290
  Groh, J., D. Klein, K. Berve, B.L. West, and R. Martini
  (See online at https://doi.org/10.1002/glia.23539)