Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson's Disease

Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2019-02, Vol.12, p.10-10
Main Authors: Lasbleiz, Christelle, Mestre-Francés, Nadine, Devau, Gina, Luquin, Maria-Rosario, Tenenbaum, Liliane, Kremer, Eric J, Verdier, Jean-Michel
Format: Article
Language:English
Subjects:
Adenoviruses
Animal cognition
Animal models
Apoptosis
CAV vectors
Deep brain stimulation
Dementia
Dihydroxyphenylalanine
Dopamine
Dopamine receptors
dopaminergic neurons
Free radicals
Gene transfer
Genes
Levodopa
Life Sciences
Movement disorders
Mutation
Neostriatum
Neurobiology
Neurodegeneration
Neurodegenerative diseases
Neurons
Neurons and Cognition
Neuroscience
Parkinson's disease
Phenotypes
primate
Substantia nigra
Transgenic animals
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Summary:Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration of L-dopa and deep brain stimulation are potent therapies, their costs, side effects and gradual loss of efficacy underlines the need to develop other approaches. Unfortunately, the lack of pertinent animal models that reproduce DA neuron loss and behavior deficits-in a timeline that mimics PD progression-has hindered the identification of alternative therapies. A complementary approach to transgenic animals is the use of nonhuman primates (NHPs) combined with the overexpression of disease-related genes using viral vectors. This approach may induce phenotypes that are not influenced by developmental compensation mechanisms, and that take into account the personality of animals. In this review article, we discuss the combination of gene transfer and NHPs to develop "genetic" models of PD that are suitable for testing therapeutic approaches.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2019.00010