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Int J Mol Sci. 2012;13(6):6883-901. doi: 10.3390/ijms13066883. Epub 2012 Jun 7.

Fragment C of tetanus toxin: new insights into its neuronal signaling pathway.

Author information

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; E-Mails: accalvo@unizar.es (A.C.C.); soligar@unizar.es (S.O.); rmanzano@unizar.es (R.M.); pilarzar@unizar.es , osta@unizar.es (P.Z.).

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:

Trk receptors; clathrin-mediated pathway; dynamin; fragment C; neurotrophin; tetanus toxin

PMID:
22837670
PMCID:
PMC3397502
DOI:
10.3390/ijms13066883
[Indexed for MEDLINE]
Free PMC Article

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