Tetanus Toxin C-Fragment: The Courier and the Cure?
Abstract
:1. Introduction
1.1. Overview
1.2. Tetanus Toxin
2. TTC as a Neuronal Retrograde Tracer and Carrier of Therapeutic Molecules
2.1. TTC as a Tracer for Neuroanatomy and Cellular Physiology
Construct | Fused Protein | Method 1 | Model (Administration); in vitro Model 2 | Reported Location/Transport, (effect) | References 3 |
---|---|---|---|---|---|
TTC-HRP | Horse radish peroxidase | CC, RPb | Mouse (IM, IP, IC) | Coated vesicles, endosomes | [13,58] |
TTC-HRP-hIgG | Horse radish peroxidase-hIgG | CC | Mouse (IM, IP) | MNs, CNS | [32] |
GO-TTC | Glucose oxidase | CC | Mouse (IM) | MN terminals, CNS | [33] |
β-Gal-TTC | β -galactosidase | RPb, ND | Mouse (IM), rat (IM), Xenopus (IM) | NMJs, MNs, CNS, 2nd and higher order neurons | [35,36,37,38,39] |
GFP-TTC | Green fluorescent protein | RP, ND, TG | Mouse (IM, IC); mouse and rat primary culture neurons, rat spinal cord MNs | MN terminals, coated vesicles, endosomes, 2nd and higher order neurons | [24,35,40,41,42,43,44,68,99] |
TTC-HEXA | β -N-acetylhexosaminidase-A | CC | Rat primary culture neurons, feline GM2 gangliosidosis neuronal culture | Endosomes, (enhances GM2 degradation - secondary lysosomes?) | [48] |
SOD1-TTC | Cu/Zn superoxide dismutase | RPb | Mouse (IM, IC); murine neuroblastoma hybrid cell line | Intra-cytoplasmic vesicles, MNs, CNS, (no protection from oxidative injury) | [52,53,59,63] |
SMN1-TTC | Survival motor neuron 1 | RPb | Rat primary culture neurons | Neuronal surface, not internalized | [63] |
CT1-TTC | Cardiotrophin-1 | RPb | Mouse and rat primary culture neurons, rat spinal cord MNs | Intra-cytoplasmic vesicles, synaptic contacts, (induces CT1-dependent cellular processes) | [68] |
Bcl-xL-GFP-TTC | B-cell lymphoma-extra large | RPb | Rat spinal cord MNs, dorsal root ganglion neurons | Internalized and transported to soma, (protects from apoptosis) | [72] |
IGF-1-TTC | Insulin-like growth factor 1 | RPb, RPi | Mouse, SOD1G93A mouse (IM, IT); mouse spinal cord MNs | Intra-cytoplasmic vesicles, MNs, CNS, (prevents muscle force decline with age, fails to improve SOD1G93A survival) | [79,80,81] |
GDNF-TTC | Glial derived neurotrophic factor | CC, RPb, RPi | Mouse (IM, IT), SOD1G93A mouse (IM); mouse neuronal cell lines, rat axotomized MNs | MNs, CNS, (protect axotomized MNs, prolongs SOD1G93A survival) | [95,96,97] |
BDNF-TTC | Brain derived neurotrophic factor | RPb | Mouse cortical neurons and neuroblastoma cell line | Internalized, (induces Akt pathway, inhibits apoptosis) | [98] |
2.2. TTC-mediated Neuronal Targeting of Metabolic Enzymes
2.3. TTC-mediated Delivery of Survival Factors, Growth Factors and Neurotrophins
3. Neuroprotective Properties of TTC Alone
4. Future Directions
5. Conclusions
Acknowledgements
References and Notes
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Toivonen, J.M.; Oliván, S.; Osta, R. Tetanus Toxin C-Fragment: The Courier and the Cure? Toxins 2010, 2, 2622-2644. https://doi.org/10.3390/toxins2112622
Toivonen JM, Oliván S, Osta R. Tetanus Toxin C-Fragment: The Courier and the Cure? Toxins. 2010; 2(11):2622-2644. https://doi.org/10.3390/toxins2112622
Chicago/Turabian StyleToivonen, Janne M., Sara Oliván, and Rosario Osta. 2010. "Tetanus Toxin C-Fragment: The Courier and the Cure?" Toxins 2, no. 11: 2622-2644. https://doi.org/10.3390/toxins2112622