Pathogenese erblicher Neuropathien: Implicationen von Komponenten des angeborenen und adaptiven Immunsystems

• Antragsteller: Professor Dr. Rudolf Martini
• Fachliche Zuordnung: Klinische Neurologie; Neurochirurgie und Neuroradiologie
• Förderung: Förderung von 2013 bis 2019
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 227548520

• Erstellungsjahr: 2020

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• 2018. Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration. EMBO J. 37
  Shashi, Vandana; Magiera, Maria M; Klein, Dennis; Zaki, Maha; Schoch, Kelly; Rudnik‐Schöneborn, Sabine; Norman, Andrew; Lopes Abath Neto, Osorio; Dusl, Marina; Yuan, Xidi; Bartesaghi, Luca; De Marco, Patrizia; Alfares, Ahmed A; Marom, Ronit; Arold, Stefan T; Guzmán‐Vega, Francisco J; Pena, Loren DM; Smith, Edward C; Steinlin, Maja; ... & Senderek, Jan
  
• 2018. Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice. The Journal of Neuroscience 38:4610-4620
  Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L.; Weis, Joachim; Katona, Istvan & Martini, Rudolf
  
• 2018. Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. Nat Commun. 9:3025
  Fledrich, R.; Abdelaal, T.; Rasch, L.; Bansal, V.; Schütza, V.; Brügger, B.; Lüchtenborg, C.; Prukop, T.; Stenzel, J.; Rahman, R. U.; Hermes, D.; Ewers, D.; Möbius, W.; Ruhwedel, T.; Katona, I.; Weis, J.; Klein, D.; Martini, R.; Brück, W.; ... & Sereda, M. W.
  
• 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. Targeting microglia attenuates neuroinflammation-related neural damage in mice carrying human PLP1 mutations. Glia. 67:277-290
  Groh, Janos; Klein, Dennis; Berve, Kristina; West, Brian L. & Martini, Rudolf
  
• 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