NDLI: Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo.

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Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo.

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Pan-neurotrophin 1: a genetically engineered neurotrophic factor displaying multiple specificities in peripheral neurons in vitro and in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Curtis, R. Acheson, A. Funakoshi, H. Yancopoulos, G. D. Glass, D. Tobkes, N. J. Ilag, L. L. Lindsay, R. M. Persson, H. Ryan, T. E.
Description	Author Affiliation: Ilag LL ( Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.);
Abstract	Pan-neurotrophin 1 (PNT-1) is a synthetic trophic factor engineered by combining active domains of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3) into an NT-3 backbone. This molecule was produced in transiently transfected COS cells or in baculovirus-infected insect cells transfected COS cells or in baculovirus-infected insect cells and subsequently purified to homogeneity. Saturation binding in embryonic spinal sensory neurons demonstrated a greater number of high-affinity binding sites for PNT-1 than for its parental molecule NT-3. PNT-1 was shown to efficiently block the chemical crosslinking of NGF, BDNF, and NT-3 to their cognate Trk receptors and to the low-affintiy NGF receptor expressed on neuronal and nonneuronal cells. PNT-1 stimulated survival and proliferation of MG87 fibroblasts expressing either TrkA, TrkB, or TrkC. PNT-1 also promoted survival of a greater number of embryonic dorsal root ganglion neurons than any of the other neurotrophins alone, and its effects were equivalent to a combination of NGF, BDNF, and NT-3. Analysis of receptor-specific neurotrophic activities demonstrated that PNT-1 efficiently rescued TrkA mRNA-containing sympathetic neurons and TrkB and TrkC mRNA-containing sensory neurons from the dorsal root and nodose ganglia. Finally, PNT-1 showed robust retrograde transport to DRG neurons in vivo after injection into the sciatic nerve. Radiolabeled PNT-1 accumulated in small-, medium-, and large-sized neurons. Coinjection with different unlabeled neurotrophins inhibited PNT-1 transport in distinct subpopulations of neurons of different sizes, suggesting that this molecule affects sensory neurons of different modalities. These results indicate that PNT-1 is a potent and multispecific neurotrophic factor that may be useful in the treatment of peripheral neurophathies and nerve damage.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	2
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Nerve Growth Factors Genetics Metabolism Pharmacology Neurons Peripheral Nerves Recombinant Fusion Proteins Animals Autoradiography Biological Transport Brain-Derived Neurotrophic Factor Cell Survival Cells, Cultured Ganglia, Spinal Cytology Iodine Radioisotopes Isotope Labeling Lumbosacral Region Nerve Tissue Proteins Neurotrophin 3 Protein Engineering Receptors, Nerve Growth Factor Classification Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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