Next Article in Journal
By-Passing Large Screening Experiments Using Sequencing as a Tool to Identify scFv Fragments Targeting Atherosclerotic Lesions in a Novel In Vivo Phage Display Selection
Previous Article in Journal
Inflammation Amplification by Versican: The First Mediator
Previous Article in Special Issue
Differential Motor Neuron Impairment and Axonal Regeneration in Sporadic and Familiar Amyotrophic Lateral Sclerosis with SOD-1 Mutations: Lessons from Neurophysiology
Article Menu

Export Article

Open AccessReview
Int. J. Mol. Sci. 2012, 13(6), 6883-6901;

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

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
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)
Full-Text   |   PDF [4043 KB, uploaded 19 June 2014]   |  


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. View Full-Text
Keywords: clathrin-mediated pathway; dynamin; fragment C; tetanus toxin; neurotrophin; Trk receptors clathrin-mediated pathway; dynamin; fragment C; tetanus toxin; neurotrophin; Trk receptors

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top