A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice.

A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Research Abstract Details 

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A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Abstract Text:

Kristin E Larsen,Susanna C Benn,Ilknur Ay,Ru-Ju Chian,Samuel A Celia,Mary P Remington,Michelle Bejarano,Meiqin Liu,Joshua Ross,Paul Carmillo,Dinah Sah,Kester A Phillips,David Sulzer,R Blake Pepinsky,Paul S Fishman,Robert H Brown,Jonathan W Francis,

Glial cell line-derived neurotrophic factor (GDNF) has shown robust neuroprotective and neuroreparative activities in various animal models of Parkinson's Disease or amyotrophic lateral sclerosis (ALS). The successful use of GDNF as a therapeutic in humans, however, appears to have been hindered by its poor bioavailability to target neurons in the central nervous system (CNS). To improve delivery of exogenous GDNF protein to CNS motor neurons, we employed chemical conjugation techniques to link recombinant human GDNF to the neuronal binding fragment of tetanus toxin (tetanus toxin fragment C, or TTC). The predominant species present in the purified conjugate sample, GDNF:TTC, had a molecular weight of approximately 80 kDa as determined by non-reducing SDS-PAGE. Like GDNF, addition of GDNF:TTC to culture media of neuroblastoma cells expressing GFRalpha-1/c-RET produced a dose-dependent increase in cellular phospho-c-RET levels. Treatment of cultured midbrain dopaminergic neurons with either GDNF or the conjugate similarly promoted both DA neuron survival and neurite outgrowth. However, in contrast to mice treated with GDNF by intramuscular injection, mice receiving GDNF:TTC revealed intense GDNF immunostaining associated with spinal cord motor neurons in fixed tissue sections. That GDNF:TTC provided neuroprotection of axotomized motor neurons in neonatal rats further revealed that the conjugate retained its GDNF activity in vivo. These results indicate that TTC can serve as a non-viral vehicle to substantially improve the delivery of functionally active growth factors to motor neurons in the mammalian CNS.

A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Publishing Authors By Initials

KE Larsen,SC Benn,I Ay,RJ Chian,SA Celia,MP Remington,M Bejarano,M Liu,J Ross,P Carmillo,D Sah,KA Phillips,D Sulzer,RB Pepinsky,PS Fishman,RH Brown,JW Francis,

For similar enzymes and coenzymes: enzymes: oxidoreductases: oxygenases: mixed function oxygenases: tyrosine 3-monooxygenase research abstracts see: enzymes and coenzymes: enzymes: oxidoreductases: oxygenases: mixed function oxygenases: tyrosine 3-monooxygenase research

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A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Brain research

VOLUME: 1120

Page Numbers: 1-12

Journal Abbreviation: Brain Res.

ISSN: 0006-8993

DAY: 3

MONTH: 10

YEAR: 2006

A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 45503

A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Keywords Mesh Terms:

KEYWORDS: Tyrosine 3-Monooxygenase

MESH TERMS: metabolism

Chemical & Substance for Abstract: A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice. Information

Substance Name: Tyrosine 3-Monooxygenase

Registry Number: EC 1.14.16.2

Grant and Affiliation Information for A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice.

AFFILIATION: Columbia University, Department of Neurology, New York, NY 10032, and Cecil B. Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA.

Country: Netherlands

AGENCY: United States NINDS

GRANT: R01 NS038679

ACRONYM: NS

MEDLINETA: Brain Res

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