Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS

被引：15

作者：

Li, Jianhong ^{[1
]}

Chian, Ru-Ju ^{[1
]}

Ay, Ilknur ^{[1
]}

Kashi, Brenda B. ^{[1
]}

Celia, Samuel A. ^{[1
]}

Tamrazian, Eric ^{[1
]}

Pepinsky, R. Blake ^{[2
]}

Fishman, Paul S. ^{[3
,4
]}

Brown, Robert H., Jr. ^{[1
]}

Francis, Jonathan W. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Dept Neurol, Cecil B Day Labr Neuromuscular Res, Charlestown, MA 02129 USA

[2] Biogenldec Inc, Cambridge Ctr 14, Cambridge, MA 02142 USA

[3] Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA

[4] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 390卷 / 03期

关键词：

Recombinant protein; GDNF; Tetanus toxin fragment C; Spinal cord; Intrathecal infusion; Intramuscular injection; TOXIN FRAGMENT-C; MOTOR-NEURON DEGENERATION; INDUCED CELL-DEATH; NEUROTROPHIC FACTOR; TETANUS TOXIN; PARKINSONS-DISEASE; EXPRESSION SYSTEM; GROWTH-FACTOR; SPINAL-CORD; MICE;

D O I：

10.1016/j.bbrc.2009.10.083

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

With a view toward improving delivery of exogenous glial cell line-derived neurotrophic factor (GDNF) to CNS motor neurons in vivo, we evaluated the bioavailability and pharmacological activity of a recombinant GDNF:tetanus toxin C-fragment fusion protein in mouse CNS. Following intramuscular injection, GDNF:TTC but not recombinant GDNF (rGDNF) produced strong GDNF immunostaining within ventral horn cells of the spinal cord. Intrathecal infusion of GDNF:TTC resulted in tissue concentrations of GDNF in lumbar spinal cord that were at least 150-fold higher than those in mice treated with rGDNF. While levels of immunoreactive choline acetyltransferase and GFR alpha-1 in lumbar cord were not altered significantly by intrathecal infusion of rGNDF, GDNF:TTC, or TTC, only rGDNF and GDNF:TTC caused significant weight loss following intracerebroventricular infusion. These studies indicate that insect cell-derived GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves delivery of GDNF to spinal cord following intramuscular- or intrathecal administration. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：947 / 951

页数：5

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