Tetanus toxin fragment C as a vector to enhance delivery of proteins to the CNS

Francis, Jonathan W.; Bastia, Elena; Matthews, Christopher C.; Parks, Deborah A.; Schwarzschild, Michael A.; Brown, Robert H.; Fishman, Paul S.

doi:10.1016/j.brainres.2004.03.007

Cited by 37 publications

(21 citation statements)

References 18 publications

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“…Following receptor‐mediated endocytosis into presynaptic terminals, the internalized toxin undergoes retrograde axonal transport back to the cell bodies of motor neurons located in the brainstem and ventral horn of the spinal cord gray matter. Once here, TeNT is transcytosed to inhibitory interneurons, where it blocks the release of inhibitory neurotransmitters that normally block the nerve impulses 3–6 …”

Section: Discussionmentioning

confidence: 99%

An immunohistochemical study on a tetanus fatal case using toxin fragment C (TTC). Should it be a useful diagnostic tool?

et al. 2009

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A 65-year-old man fell in his garden and sustained a right pre-radial cutaneous laceration associated with a Colles' fracture. His status for tetanus immunization was uncertain; so a course of antitetanus treatment was immediately started. Two days after admission the man suddenly developed severe nucal pain, rigidity and dysphagia. A brain CT scan was negative. His condition progressively worsened and then he developed trismus. Cultures from the wound were negative for Clostridium tetani; the CSF analysis was negative. On the 9th day after admission, the man died. A presumptive clinical diagnosis of tetanus was made. Autopsy was performed 24 h after death. An immunohistochemical study was conducted with an antibody directed against tetanus toxin fragment C (TTC). By immunohistochemical evaluation, large motor neurons in the ventral horn were immunopositive for TTC. High power magnification of the ventral horn of spinal cord gray matter samples showed TTC immunoreactivity in motor neuron axons and cell bodies, using a confocal laser scanning microscope. The correct diagnosis could be established on the basis of pathological examination with TTC immunostaining.

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Section: Discussionmentioning

confidence: 99%

An immunohistochemical study on a tetanus fatal case using toxin fragment C (TTC). Should it be a useful diagnostic tool?

et al. 2009

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“…Elevated levels of SOD1 displayed cyto-protective effects in neurological disorders caused by free radical toxicity [175][176][177]. In hippocampal neurons, a H C T/SOD1 fusion protein was successfully internalized and retrogradely transported, maintaining its enzymatic activity after transport [56,178,179]. A second study generated a β-galactosidase gene (lacZ)-H C T fusion protein, which was able to undergo retrograde trafficking across synapses in vivo [180].…”

Section: Protein and Gene Transfer Via Tentmentioning

confidence: 97%

Uptake and transport of clostridial neurotoxins

Schmieg

Bercsényi

Schiavo

2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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“…Recombinant SOD1-TTC fusion protein used for a previous study [52] was also the first one used to evaluate the distribution and uptake of TTC-coupled protein after direct intracerebral injection [58] and cerebrospinal fluid infusion [59]. Although the metabolic effects of the SOD1 were not evaluated in the first study, TTC-SOD1 fusion protein showed vastly superior retention within brain tissue than SOD1 alone (or bovine serum albumin), and were distributed in synaptic and endosomal pattern suggesting retrograde transport [58]. In the latter study, it was demonstrated that TTC improved the stability of the SOD1, consistent with internalization by neurons.…”

Section: Ttc As a Neuronal Retrograde Tracer And Carrier Of Therapmentioning

confidence: 99%

Tetanus Toxin C-Fragment: The Courier and the Cure?

Toivonen

Oliván

Osta

2010

Toxins

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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.

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Tetanus toxin fragment C as a vector to enhance delivery of proteins to the CNS

Cited by 37 publications

References 18 publications

An immunohistochemical study on a tetanus fatal case using toxin fragment C (TTC). Should it be a useful diagnostic tool?

An immunohistochemical study on a tetanus fatal case using toxin fragment C (TTC). Should it be a useful diagnostic tool?

Uptake and transport of clostridial neurotoxins

Tetanus Toxin C-Fragment: The Courier and the Cure?

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