Neuroprotective gene therapy for Parkinson's disease.

Détails

ID Serval
serval:BIB_C359A37C80BD
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Neuroprotective gene therapy for Parkinson's disease.
Périodique
Current Gene Therapy
Auteur(s)
Tenenbaum L., Chtarto A., Lehtonen E., Blum D., Baekelandt V., Velu T., Brotchi J., Levivier M.
ISSN
1566-5232 (Print)
ISSN-L
1566-5232
Statut éditorial
Publié
Date de publication
2002
Peer-reviewed
Oui
Volume
2
Numéro
4
Pages
451-483
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Résumé
Parkinson's disease (PD) is a neurodegenerative disease characterised by a progressive loss of the dopaminergic neurones in the substantia nigra pars compacta. Accumulating evidence indicates that apoptosis contributes to neuronal cell death in PD patients' brain. Excitotoxicity, oxidative stress, and mitochondrial respiratory failure are thought to be the key inducers of the apoptotic cascade. Even though the initial cause and the mechanism of degeneration are poorly understood, neuroprotection can be achieved by interfering with neuronal cell death either directly or by preventing neuronal dysfunction. Potential agents for neuroprotection are neurotrophic factors, inhibitors of apoptosis or anti-oxidative agents. However, the existence of the blood-brain barrier precludes systemic delivery of these factors. In situ gene delivery provides strategies for local and sustained administration of protective factors at physiologically relevant doses. Viral vectors mediating stable gene expression in the central nervous system exist and are still under development. Efficacy of these vectors has repeatedly been demonstrated in the animal models both ex vivo and in vivo. Ex vivo gene delivery could furthermore be combined with cell replacement therapies by transplanting genetically modified cells compensating for the lost neuronal cell population in order to provide neuroprotection to both the grafted cells and degenerating host neurones. However, several aspects of gene transfer, such as uncontrolled diffusion, axonal transport, unpredictable site of integration and immunological responses, still raise safety concerns and justify further development of viral and non-viral vectors as well as genetic elements with tightly controlled gene expression. Various relevant animal models for Parkinson's disease are available for the evaluation of gene therapy strategies. These include induction of cell death in specific neurone population through administration of toxins either directly in the brain or systemically, as well as transgenic mice expressing human disease-associated mutations.
Mots-clé
Animals, Cell Death, Disease Models, Animal, Gene Expression Regulation, Genetic Therapy, Genetic Vectors, Humans, Parkinson Disease/pathology, Parkinson Disease/therapy
Pubmed
Création de la notice
20/01/2008 18:35
Dernière modification de la notice
03/03/2018 21:11
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