DELIVERY OF RECOMBINANT TETANUS-SUPEROXIDE DISMUTASE PROTEINS TO CENTRAL-NERVOUS-SYSTEM NEURONS BY RETROGRADE AXONAL-TRANSPORT

The nontoxic C fragment of tetanus toxin (TC) can transport other prot eins from the circulation to central nervous system (CNS) motor neuron s. Increased levels of CuZn superoxide dismutase (SOD) are protective in experimental models of stroke and Parkinson's disease, whereas muta tions in SOD can cause motor neuron disease. We have linked TC to SOD and purified the active recombinant proteins in both the TC-SOD and SO D-TC orientations. Light microscopic immunohistochemistry and quantita tive enzyme-linked immunosorbant assays (ELISA) of mouse brainstem, af ter intramuscular injection, demonstrate that the fusion proteins unde rgo retrograde axonal transport and transsynaptic transfer as efficien tly as TC alone. (C) 1997 Academic Press.