Tetanus toxin C-fragment: the courier and the cure?

Toxins (Basel). 2010 Nov;2(11):2622-44. doi: 10.3390/toxins2112622. Epub 2010 Oct 29.


In many neurological disorders strategies for a specific delivery of a biological activity from the periphery to the central nervous system (CNS) remains a considerable challenge for successful therapy. Reporter assays have established that the non-toxic C-fragment of tetanus toxin (TTC), provided either as protein or encoded by non-viral naked DNA plasmid, binds pre-synaptic motor neuron terminals and can facilitate the retrograde axonal transport of desired therapeutic molecules to the CNS. Alleviated symptoms in animal models of neurological diseases upon delivery of therapeutic molecules offer a hopeful prospect for TTC therapy. This review focuses on what has been learned on TTC-mediated neuronal targeting, and discusses the recent discovery that, instead of being merely a carrier molecule, TTC itself may well harbor neuroprotective properties.

Keywords: gene therapy; motor neuron disease; neurodegenerative disease; retrograde transport; tetanus toxin C-fragment; therapeutic molecules.

Publication types

  • Review

MeSH terms

  • Animals
  • Axonal Transport / drug effects*
  • Disease Models, Animal
  • Gene Targeting
  • Genetic Therapy
  • Humans
  • Molecular Targeted Therapy
  • Motor Neuron Disease / drug therapy
  • Motor Neuron Disease / genetics
  • Motor Neurons / drug effects*
  • Neural Pathways / drug effects*
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / genetics
  • Neuromuscular Junction
  • Neuroprotective Agents
  • Peptide Fragments / genetics
  • Peptide Fragments / therapeutic use*
  • Presynaptic Terminals / drug effects*
  • Tetanus Toxin / genetics
  • Tetanus Toxin / therapeutic use*


  • Neuroprotective Agents
  • Peptide Fragments
  • Tetanus Toxin
  • tetanus toxin fragment C