Abstract: When Clostridium tetani was discovered and identified as a Gram-positive anaerobic bacterium of the genus Clostridium, the possibility of turning its toxin into a valuable biological carrier to ameliorate neurodegenerative processes was inconceivable. However, the non-toxic carboxy-terminal fragment of the tetanus toxin heavy chain (fragment C) can be retrogradely transported to the central nervous system; therefore, fragment C has been used as a valuable biological carrier of neurotrophic factors to ameliorate neurodegenerative processes. More recently, the neuroprotective properties of fragment C have also been described in vitro and in vivo, involving the activation of Akt kinase and extracellular signal-regulated kinase (ERK) signaling cascades through neurotrophin tyrosine kinase (Trk) receptors. Although the precise mechanism of the molecular internalization of fragment C in neuronal cells remains unknown, fragment C could be internalized and translocated into the neuronal cytosol through a clathrin-mediated pathway dependent on proteins, such as dynamin and AP-2. In this review, the origins, molecular properties and possible signaling pathways of fragment C are reviewed to understand the biochemical characteristics of its intracellular and synaptic transport.
This is an open access article distributed under the
Creative Commons Attribution License which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
Export to BibTeX
MDPI and ACS Style
Calvo, A.C.; Oliván, S.; Manzano, R.; Zaragoza, P.; Aguilera, J.; Osta, R. Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway. Int. J. Mol. Sci. 2012, 13, 6883-6901.
Calvo AC, Oliván S, Manzano R, Zaragoza P, Aguilera J, Osta R. Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway. International Journal of Molecular Sciences. 2012; 13(6):6883-6901.
Calvo, Ana C.; Oliván, Sara; Manzano, Raquel; Zaragoza, Pilar; Aguilera, José; Osta, Rosario. 2012. "Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway." Int. J. Mol. Sci. 13, no. 6: 6883-6901.