CAV-2-Mediated GFP and LRRK2G2019S Expression in the Macaca fascicularis Brain

Parkinson's disease is characterized by motor and nonmotor symptoms that gradually appears as consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Currently, no treatment can slow Parkinson’s disease progression. Inasmuch, there is a need to develop a...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2020-03, Vol.13, p.49-49
Main Authors: di Caudo, Carla, Martínez-Valbuena, Ivan, Mundiñano, Iñaki-Carril, Gennetier, Aurelie, Hernandez, Maria, Carmona-Abellan, Mar, Marcilla Garcia, Irene, Kremer, Eric J., Luquin, Rosario
Format: Article
Language:English
Subjects:
Adenoviruses
Animal models
Animals
Artificial chromosomes
Axonal transport
Brain
CAV-2
Cell death
Cytomegalovirus
Disease
Dopamine receptors
Expression vectors
Gene transfer
GFP
Kinases
Leucine
LRRK2
LRRK2 protein
M. fascicularis
Macaca fascicularis
Movement disorders
Mutation
Neurodegeneration
Neurodegenerative diseases
Neuropathology
Neuroscience
Parkinson's disease
Proteins
Retrograde transport
Studies
Substantia nigra
Surgery
Tropism
viral vectors
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Summary:Parkinson's disease is characterized by motor and nonmotor symptoms that gradually appears as consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Currently, no treatment can slow Parkinson’s disease progression. Inasmuch, there is a need to develop animal models that can be used to understand the pathophysiological mechanisms underlying dopaminergic neuron death. The initial goal of this study was to determine if canine adenovirus type 2 (CAV-2) vectors are effective gene transfer tools in the monkey brain. A second objective was to explore the possibility of developing a large nonhuman primate that expresses one the most common genetic mutation causing Parkinson’s disease. Our studies demonstrate the neuronal tropism, retrograde transport, biodistribution, and efficacy of CAV-2 vectors expressing GFP and leucine-rich repeat kinase 2 (LRRK2G2019S) in the Macaca fascicularis brain. Our data also suggest that following optimization CAV-2-mediated LRRK2G2019S expression could help us model the neurodegenerative processes of this genetic subtype of Parkinson’s disease in monkeys.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2020.00049