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Int. J. Mol. Sci. 2012, 13(6), 6883-6901; doi:10.3390/ijms13066883
Review

Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway

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1 LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-I3A, Aragonese Institute of Health Sciences (IACS), University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain 2 Institute of Neurosciences, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona (UAB), Center of Biomedical Research Network in Neurodegenerative Diseases (CIBERNET), 08193, Cerdanyola del Vallès, Spain
* Author to whom correspondence should be addressed.
Received: 28 March 2012 / Revised: 8 May 2012 / Accepted: 23 May 2012 / Published: 7 June 2012
(This article belongs to the Special Issue Studies of Motor Molecules)
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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.
Keywords: clathrin-mediated pathway; dynamin; fragment C; tetanus toxin; neurotrophin; Trk receptors clathrin-mediated pathway; dynamin; fragment C; tetanus toxin; neurotrophin; Trk receptors
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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