Abstract
No other exogenous protein enters the central nervous system from the circulation as readily as tetanus toxin. We examined the capability of the non-toxic binding fragment of tetanus toxin (C-Fragment) so serve as a vehicle for transport of other proteins into the mouse CNS. Using periodate oxidation of the enzyme horseradish peroxidase (HRP), we synthesized two separate macromolecular complexes, one containing C-fragment and HRP, and the other C-fragment, HRP and a third "test" protein-human IgG. The distribution of C-fragment-HRP was typical of blood borne proteins including native C-fragment, with labeling of all neurons with known projections outside the blood-brain barrier, particularly large spinal motoneurons. C-fragment-HRP conjugates showed superior neuronal labeling to over 100-fold greater quantities of free HRP. Complexes containing C-fragment, HRP and human IgG were internalized by neurons from both intramuscular and intraperitoneal injections. The efficiency of neuronal uptake of IgG in the C-fragment conjugated form was enhanced over 40-fold compared to free IgG. Linkage of a large protein to C-fragment probably leads to enhanced endocytosis of that protein by neuronal terminals projecting outside the blood-brain barrier. C-fragment can serve as a vehicle to allow selected proteins to bypass the barrier and enter the CNS.
Original language | English (US) |
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Pages (from-to) | 311-325 |
Number of pages | 15 |
Journal | Journal of the Neurological Sciences |
Volume | 98 |
Issue number | 2-3 |
DOIs | |
State | Published - Sep 1990 |
Externally published | Yes |
Keywords
- Axonal transport
- Blood-brain barrier
- C-fragment
- Endocytosis
- Horseradish peroxidase
- Motoneurons
- Tetanus toxin
ASJC Scopus subject areas
- Neurology
- Clinical Neurology