Pharmacological actions of nerve growth factor-transferrin conjugate on the central nervous system.
Transferrin (Tf) undergoes receptor-mediated transport through the blood-brain barrier in vivo. This property allows transferrin to act as a vector for drug transport to the brain. The present investigation examines both the profile of brain delivery of nerve growth factor (NGF)-transferrin conjugate, and its therapeutic effects on CNS neurodegeneration, which affect locomotion and memory. Delivery of NGF-Tf conjugate to the brain was measured and found to be 0.075% of the injected dose per gram of brain, which is 5-fold higher than that of biotin-NGF. The increased delivery using the NGF-Tf conjugate can be attributed to an increased BBB permeability surface area product, which is about 8-fold higher than that of biotin-NGF. Intravenous injection of biotin-NGF/Tf-avidin conjugate significantly increased neuronal survival in the substantia nigra of a Parkinson's disease mouse model. In addition, this conjugate also improved recognition and memory in Alzheimer's disease rat model. In summary, these results demonstrate that using transferrin as a delivery vector is effective in targeting NGF to the central nervous system (CNS), and may optimize the therapy of age-related neurodegenerative diseases.
Liao
G S
GS
Snake Venom Research Institute, Guangxi Medical University, Nanning, People's Republic of China. shanl@public.nn.gx.cn
Li
X B
XB
Zhang
C Y
CY
Shu
Y Y
YY
Tang
S X
SX
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001812:Blood-Brain Barrier; D004337:Drug Carriers; D007275:Injections, Intravenous; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D023421:Models, Animal; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects; D014168:Transferrin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D004337:Drug Carriers; D014168:Transferrin; D020932:Nerve Growth Factor