Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/13594
Title: Minimal essential length of Clostridium botulinum C3 peptides to enhance neuronal regenerative growth and connectivity in a non-enzymatic mode
Authors: Loske, Peter
Boato, Francesco
HENDRIX, Sven 
Piepgras, Johannes
Just, Ingo
Ahnert-Hilger, Gudrun
Hoeltje, Markus
Issue Date: 2012
Publisher: WILEY-BLACKWELL
Source: JOURNAL OF NEUROCHEMISTRY, 120 (6), p. 1084-1096
Abstract: C3 ADP-ribosyltransferase is a valuable tool to study Rho-dependent cellular processes. In the current study we investigated the impact of enzyme-deficient peptides derived from Clostridium botulinum C3 transferase in the context of neuronal process elongation and branching, synaptic connectivity, and putative beneficial effects on functional outcome following traumatic injury to the CNS. By screening a range of peptidic fragments, we identified three short peptides from C3bot that promoted axon and dendrite outgrowth in cultivated hippocampal neurons. Furthermore, one of these fragments, a 26-amino acid peptide covering the residues 156181 enhanced synaptic connectivity in primary hippocampal culture. This peptide was also effective to foster axon outgrowth and re-innervation in organotypical brain slice culture. To evaluate the potential of the 26mer to foster repair mechanisms after CNS injury we applied this peptide to mice subjected to spinal cord injury by either compression impact or hemisection. A single local administration at the site of the lesion improved locomotor recovery. In addition, histological analysis revealed an increased serotonergic input to lumbar motoneurons in treated compared with control mice. Pull-down assays showed that lesion-induced up-regulation of RhoA activity within the spinal cord was largely blocked by C3bot peptides despite the lack of enzymatic activity.
Notes: [Hoeltje, Markus] Charite, Inst Integrat Neuroanat, Ctr Anat, D-10115 Berlin, Germany. [Boato, Francesco; Hendrix, Sven] Hasselt Univ, Dept Morphol, Hasselt, Belgium. [Boato, Francesco; Hendrix, Sven] Hasselt Univ, Inst Biomed, Hasselt, Belgium. [Just, Ingo] Hannover Med Sch MHH, Inst Toxicol, Hannover, Germany.
Keywords: Biochemistry & Molecular Biology; Neurosciences;C3 transferase; regeneration; RhoA; spinal cord injury
Document URI: http://hdl.handle.net/1942/13594
ISSN: 0022-3042
e-ISSN: 1471-4159
DOI: 10.1111/j.1471-4159.2012.07657.x
ISI #: 000301112500020
Category: A1
Type: Journal Contribution
Validations: ecoom 2013
Appears in Collections:Research publications

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