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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Published inFrontiers in molecular neuroscience Vol. 13; p. 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 Journal Article
LanguageEnglish
Published Lausanne Frontiers Research Foundation 25.03.2020
Frontiers Media S.A
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.
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These authors share senior authorship
These authors have contributed equally to this work
Reviewed by: Martin Levesque, Laval University, Canada; Rosario Moratalla, Spanish National Research Council, Spain
Edited by: Serena Carra, University of Modena and Reggio Emilia, Italy
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2020.00049