Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 13, Issue 6, Pages 6883-6901Publisher
MDPI
DOI: 10.3390/ijms13066883
Keywords
clathrin-mediated pathway; dynamin; fragment C; tetanus toxin; neurotrophin; Trk receptors
Funding
- Spanish Ministerio de Educacion y Ciencia [SAF2009-13626]
- Caja Navarra: Tu eliges, tu decides
- Fondo de Investigacion Sanitaria of Spain [PI10/0178]
- ALS Association [S54406]
- Ministerio de Ciencia e Innovacion INNPACTO [IPT-2011-1091-900000]
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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.
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