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Titolo:
Adeno-associated virus-mediated delivery of glial cell line-derived neurotrophic factor protects motor neuron-like cells from apoptosis
Autore:
Keir, SD; Xiao, X; Li, J; Kennedy, PGE;
Indirizzi:
Univ Glasgow, Dept Neurol, Inst Neurol Sci, So Gen Hosp, Glasgow G41 5TF, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G41 5TF ow G41 5TF, Lanark, Scotland Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA USA Univ Pittsburgh Pittsburgh PA USA ol Genet & Biochem, Pittsburgh, PA USA Univ Pittsburgh, Gene Therapy Ctr, Pittsburgh, PA USA Univ Pittsburgh Pittsburgh PA USA , Gene Therapy Ctr, Pittsburgh, PA USA
Titolo Testata:
JOURNAL OF NEUROVIROLOGY
fascicolo: 5, volume: 7, anno: 2001,
pagine: 437 - 446
SICI:
1355-0284(200110)7:5<437:AVDOGC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-TRANSFER; EFFICIENT TRANSDUCTION; TYROSINE KINASE; VECTORS; GDNF; RECEPTOR; EXPRESSION; TYPE-2; BRAIN; CORECEPTOR;
Keywords:
amyotrophic lateral sclerosis; adeno-associated virus; glial cell line-derived neurotrophic factor; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Keir, SD Univ Glasgow, Dept Neurol, Inst Neurol Sci, So Gen Hosp, Glasgow G41 5TF, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G41 5TF F, Lanark, Scotland
Citazione:
S.D. Keir et al., "Adeno-associated virus-mediated delivery of glial cell line-derived neurotrophic factor protects motor neuron-like cells from apoptosis", J NEUROVIRO, 7(5), 2001, pp. 437-446

Abstract

Motor neuron disorders including amyotrophic lateral sclerosis may benefitfrom the induction of neurotrophic factors such as glial cell line-derivedneurotrophic factor (GDNF) that are known to be trophic and protective formotor 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 12:54:02