Molekulare Strategien zur Unterstützung der funktionalen Reinnervation des mit Zellimplantation behandelten Harnröhrensphinkters unter Verwendung eines neuen auf p-53 basierenden Ansatzes.

• Antragsteller: Professor Dr. Simone Di Giovanni
• Fachliche Zuordnung: Reproduktionsmedizin, Urologie
• Förderung: Förderung von 2012 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 190473765

• Erstellungsjahr: 2016

Zusammenfassung der Projektergebnisse

In summary we found that p53-MDM2/4-IGF1 signaling is essential for axonal regeneration of corticospinal and raphespinal axons after a SCI. Axonal regeneration requires p53 and IGF1. In fact IGF1 is required for p53 dependent enhancement of axonal sprouting and regeneration of 5-HT raphespinal and CST axons after SCI. Furthermore, Nutlin-3 delivery that enhances p53-IGF1 pathway, promotes recovery of sensorimotor and urinary impairments. Ultimately, these studies provided a novel understanding of p53-dependent pathways and of the role of p53-IGF1 in the control of axonal sprouting and regeneration as well as functional recovery after SCI.

Projektbezogene Publikationen (Auswahl)

• P53 regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury. J Neurosci. 2012 Oct 3;32(40):13956-70
  Floriddia, Elisa M.; Rathore, Khizr I.; Tedeschi, Andrea; Quadrato, Giorgia; Wuttke, Anja; Lueckmann, Jan-Matthis; Kigerl, Kristina A.; Popovich, Phillip G. & Di Giovanni, Simone
  
• The transcription factor serum response factor (SRF) stimulates axon regeneration through cytoplasmic localization and cofilin interaction. J Neurosci. 2013. Nov 27;33(48):18836-48
  Stern, Sina; Haverkamp, Stephanie; Sinske, Daniela; Tedeschi, Andrea; Naumann, Ulrike; Di Giovanni, Simone; Kochanek, Stefan; Nordheim, Alfred & Knöll, Bernd
  
• The tumor suppressor p53 fine-tunes ROS levels and neurogenesis via PI3K signaling. J Neurosci. 2013 Sep 4;33(36):14318-30
  Forsberg, Kirsi; Wuttke, Anja; Quadrato, Giorgia; Chumakov, Peter M.; Wizenmann, Andrea & Di Giovanni, Simone
  
• DNA methylation temporal profiling following peripheral versus central nervous system axotomy. Scientific Data 11 Sept 2014
  Lindner, Ricco; Puttagunta, Radhika; Nguyen, Tuan & Di Giovanni, Simone
  
• PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system. Nature Comm. 2014 Apr 1;5:3527
  Puttagunta, Radhika; Tedeschi, Andrea; Sória, Marilia Grando; Hervera, Arnau; Lindner, Ricco; Rathore, Khizr I.; Gaub, Perrine; Joshi, Yashashree; Nguyen, Tuan; Schmandke, Antonio; Laskowski, Claudia J.; Boutillier, Anne-Laurence; Bradke, Frank & Di Giovanni, Simone
  
• The MDM4/MDM2-p53-IGF1 axis controls axonal regeneration, sprouting and functional recovery after CNS injury. Brain. 2015 Jul;138(Pt 7):1843-62
  Joshi, Yashashree; Sória, Marília Grando; Quadrato, Giorgia; Inak, Gizem; Zhou, Luming; Hervera, Arnau; Rathore, Khizr I.; Elnaggar, Mohamed; Cucchiarini, Magali; Marine, Jeanne Christophe; Puttagunta, Radhika & Di Giovanni, Simone