Adeno-associated virus-mediated delivery of glial cell line-derived neurotrophic factor protects motor neuron-like cells from apoptosis

Keir, S.D., Xiao, X., Li, J. and Kennedy, P.G.E. (2001) Adeno-associated virus-mediated delivery of glial cell line-derived neurotrophic factor protects motor neuron-like cells from apoptosis. Journal of Neurovirology, 7(5), pp. 437-446. (doi: 10.1080/135502801753170291)

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Abstract

Motor neuron disorders including amyotrophic lateral sclerosis may benefit from the induction of neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) that are known to be trophic and protective for motor neurons. However, the application of such factors is limited by an inability to successfully target their expression in the nervous system. In this study we investigate the potential of using adeno-associated virus (AAV) as a vector for gene delivery into motor neuron-like cells. In initial experiments on the motor neuron cell line NSC-19 using a recombinant AAV vector expressing the reporter gene beta-galactosidase (AAV-LacZ), we successfully demonstrate the utility of AAV for gene transfer. In addition, a recombinant AAV vector expressing GDNF was shown to express and secrete high levels of the neurotrophic factor into the surrounding media of NSC-19 infected cells. Finally, the AAV-GDNF vector is demonstrated to act in a neuroprotective fashion. Withdrawal of trophic support from NSC-19 cells through serum deprivation results in a subsequent increase in the number of cells entering apoptosis. However, the percentage of apoptotic cells are significantly reduced in cells infected with the AAV-GDNF vector, as compared to AAV-LacZ or uninfected controls. This work demonstrates the potential of using AAV as a vector in motor neuron-like cells and should prove important in devising future gene therapy strategies for the treatment of in vivo motor neuron disorders.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Peter
Authors: Keir, S.D., Xiao, X., Li, J., and Kennedy, P.G.E.
Subjects:R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Neurovirology
Publisher:Springer
ISSN:1355-0284
ISSN (Online):1538-2443

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