The role of cGMP-GKI signalling in spinal cord axonal sprouting and regeneration following injury
Zusammenfassung der Projektergebnisse
In summary we found that cGMP-GKI signaling is essential for axonal regeneration of DRG sensory axons projecting into the dorsal columns after a SCI. However, cGMP-GKI axis is not important for axonal sprouting or regeneration of 5-HT raphespinal axons or CST and does not affect retraction or die-back of CST fibers, and it does not affect functional recovery after SCI. P53 that is upstream of cGMP-GKI, is required for functional recovery, axonal sprouting and regeneration of 5-HT raphespinal axons and limits CST retraction after SCI. However, the main mechanisms downstream these effects is IGF1 and not cGMP-cGKI. In fact IGF1 is required for p53 dependent enhancement of axonal sprouting and regeneration of 5-HT raphespinal and CST axons after SCI. Ultimately, these studies provided a novel understanding of p53-dependent pathways and of the role of cGMP-cGKI in the control of axonal sprouting and regeneration after SCI.
Projektbezogene Publikationen (Auswahl)
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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
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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
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The tumor suppressor p53 fine-tunes ROS levels and neurogenesis via PI3K signaling. J Neurosci. 2013 Sep 4;33(36):14318-30
Forsberg K, Wuttke A, Quadrato G, Chumakov PM, Wizenmann A, and Di Giovanni S
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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
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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
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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
