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Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease.
Neurobiol Dis. 2004 Nov; 17(2):283-9.ND

Abstract

Viral delivery of glial cell line-derived neurotrophic factor (GDNF) currently represents one of the most promising neuroprotective strategies for Parkinson's Disease (PD). However, the effect of this neurotrophic factor has never been tested in the newly available genetic models of PD based on the viral expression of mutated alpha-synuclein. In this study, we evaluated the ability of lentiviral vectors coding for GDNF (lenti-GDNF) to prevent nigral dopaminergic degeneration associated with the lentiviral mediated expression of the A30P mutant human alpha-synuclein (lenti-A30P). This virally based rat model develops a progressive and selective loss of dopamine neurons associated with the appearance of alpha-synuclein containing inclusions, thus recapitulating the major hallmarks of PD. Lenti-GDNF was injected in the substantia nigra 2 weeks before nigral administration of lenti-A30P. Although a robust expression of GDNF was observed in the whole nigrostriatal pathway due to retrograde and/or anterograde transport, lenti-GDNF did not prevent the alpha-synuclein-induced dopaminergic neurodegeneration in the lentiviral-based genetic rat model of PD. These results suggest that sustained GDNF treatment cannot modulate the cellular toxicity related to abnormal folded protein accumulation as mutated human alpha-synuclein.

Authors+Show Affiliations

Institute of Neuroscience, Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland. christophe.lobianco@epfl.chNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15474365

Citation

Lo Bianco, C, et al. "Lentiviral Nigral Delivery of GDNF Does Not Prevent Neurodegeneration in a Genetic Rat Model of Parkinson's Disease." Neurobiology of Disease, vol. 17, no. 2, 2004, pp. 283-9.
Lo Bianco C, Déglon N, Pralong W, et al. Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiol Dis. 2004;17(2):283-9.
Lo Bianco, C., Déglon, N., Pralong, W., & Aebischer, P. (2004). Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiology of Disease, 17(2), 283-9.
Lo Bianco C, et al. Lentiviral Nigral Delivery of GDNF Does Not Prevent Neurodegeneration in a Genetic Rat Model of Parkinson's Disease. Neurobiol Dis. 2004;17(2):283-9. PubMed PMID: 15474365.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. AU - Lo Bianco,C, AU - Déglon,N, AU - Pralong,W, AU - Aebischer,P, PY - 2003/12/02/received PY - 2004/04/06/revised PY - 2004/06/16/accepted PY - 2004/10/12/pubmed PY - 2004/12/22/medline PY - 2004/10/12/entrez SP - 283 EP - 9 JF - Neurobiology of disease JO - Neurobiol Dis VL - 17 IS - 2 N2 - Viral delivery of glial cell line-derived neurotrophic factor (GDNF) currently represents one of the most promising neuroprotective strategies for Parkinson's Disease (PD). However, the effect of this neurotrophic factor has never been tested in the newly available genetic models of PD based on the viral expression of mutated alpha-synuclein. In this study, we evaluated the ability of lentiviral vectors coding for GDNF (lenti-GDNF) to prevent nigral dopaminergic degeneration associated with the lentiviral mediated expression of the A30P mutant human alpha-synuclein (lenti-A30P). This virally based rat model develops a progressive and selective loss of dopamine neurons associated with the appearance of alpha-synuclein containing inclusions, thus recapitulating the major hallmarks of PD. Lenti-GDNF was injected in the substantia nigra 2 weeks before nigral administration of lenti-A30P. Although a robust expression of GDNF was observed in the whole nigrostriatal pathway due to retrograde and/or anterograde transport, lenti-GDNF did not prevent the alpha-synuclein-induced dopaminergic neurodegeneration in the lentiviral-based genetic rat model of PD. These results suggest that sustained GDNF treatment cannot modulate the cellular toxicity related to abnormal folded protein accumulation as mutated human alpha-synuclein. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/15474365/Lentiviral_nigral_delivery_of_GDNF_does_not_prevent_neurodegeneration_in_a_genetic_rat_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(04)00149-4 DB - PRIME DP - Unbound Medicine ER -