Kordower J H, Charles V, Bayer R, Bartus R T, Putney S, Walus L R, Friden P M
Department of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL 60612.
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9077-80. doi: 10.1073/pnas.91.19.9077.
Intrastriatal injections of quinolinic acid induce a pattern of neuronal degeneration similar to that seen in Huntington disease. In the present study, nerve growth factor (NGF) crossed the blood-brain barrier in a dose-dependent fashion following intravenous infusion when conjugated to an antibody directed against the transferrin receptor (OX-26). Intravenous injections of the OX-26-NGF conjugate selectively prevented the loss of striatal choline acetyltransferase-immunoreactive neurons which normally occurs following quinolinic acid administration relative to control rats receiving vehicle or a nonconjugated mixture of OX-26 and NGF. These data demonstrate that a neurotrophic factor-antibody conjugate can prevent the degeneration of central NGF-responsive neurons following systemic administration.
纹状体内注射喹啉酸会引发一种与亨廷顿病中所见相似的神经元变性模式。在本研究中，当与针对转铁蛋白受体的抗体（OX - 26）偶联时，神经生长因子（NGF）在静脉输注后以剂量依赖的方式穿过血脑屏障。相对于接受载体或OX - 26与NGF非偶联混合物的对照大鼠，静脉注射OX - 26 - NGF偶联物可选择性地防止喹啉酸给药后通常会发生的纹状体胆碱乙酰转移酶免疫反应性神经元的丧失。这些数据表明，一种神经营养因子 - 抗体偶联物在全身给药后可防止中枢NGF反应性神经元的变性。
