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 proteins from the circulation to central nervous system (CNS) motor neurons. Increased levels of CuZn superoxide dismutase (SOD) are protective in experimental models of stroke and Parkinson's disease, whereas mutations 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 SOD-TC orientations. Light microscopic immunohistochemistry and quantitative enzyme-linked immunosorbant assays (ELISA) of mouse brainstem, after intramuscular injection, demonstrate that the fusion proteins undergo retrograde axonal transport and transsynaptic transfer as efficiently as TC alone.
Figueiredo
D M
DM
Department of Biochemistry, Imperial College, London, United Kingdom.
Hallewell
R A
RA
Chen
L L
LL
Fairweather
N F
NF
Dougan
G
G
Savitt
J M
JM
Parks
D A
DA
Fishman
P S
PS
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001933:Brain Stem / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology; D011817:Rabbits; D011994:Recombinant Proteins / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D013744:Tetanus Toxin / Q000032:analysis / Q000235:genetics / Q000493:pharmacokinetics*
D011994:Recombinant Proteins; D013744:Tetanus Toxin; D013482:Superoxide Dismutase