title: Fragment C of tetanus toxin: new insights into its neuronal signaling pathway.
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.
authors: 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.
authors: Ana C
authors: AC
authors: Calvo
authors: 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.
authors: Sara
authors: S
authors: Oliván
authors: 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.
authors: Raquel
authors: R
authors: Manzano
authors: 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.
authors: Pilar
authors: P
authors: Zaragoza
authors: 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.
authors: José
authors: J
authors: Aguilera
authors: 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.
authors: Rosario
authors: R
authors: Osta
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D003017:Clostridium tetani / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013744:Tetanus Toxin / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases