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Exogenous LRRK2G2019S induces parkinsonian-like pathology in a nonhuman primate.
Mestre-Francés, Nadine; Serratrice, Nicolas; Gennetier, Aurélie; Devau, Gina; Cobo, Sandra; Trouche, Stéphanie G; Fontès, Pascaline; Zussy, Charleine; De Deurwaerdere, Philippe; Salinas, Sara; Mennechet, Franck Jd; Dusonchet, Julien; Schneider, Bernard L; Saggio, Isabella; Kalatzis, Vasiliki; Luquin-Piudo, M Rosario; Verdier, Jean-Michel; Kremer, Eric J.
Afiliación
  • Mestre-Francés N; MMDN, University of Montpellier, Ecole Pratique des Hautes Etudes, INSERM, PSL University, Montpellier, France.
  • Serratrice N; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
  • Gennetier A; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
  • Devau G; MMDN, University of Montpellier, Ecole Pratique des Hautes Etudes, INSERM, PSL University, Montpellier, France.
  • Cobo S; MMDN, University of Montpellier, Ecole Pratique des Hautes Etudes, INSERM, PSL University, Montpellier, France.
  • Trouche SG; MMDN, University of Montpellier, Ecole Pratique des Hautes Etudes, INSERM, PSL University, Montpellier, France.
  • Fontès P; MMDN, University of Montpellier, Ecole Pratique des Hautes Etudes, INSERM, PSL University, Montpellier, France.
  • Zussy C; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
  • De Deurwaerdere P; Institut des Matériaux Jean Rouxel, CNRS, Bordeaux, France.
  • Salinas S; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
  • Mennechet FJ; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
  • Dusonchet J; Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Schneider BL; Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Saggio I; Department of Biology and Biotechnology "C. Darwin," Sapienza University of Rome, Rome, Italy.
  • Kalatzis V; Pasteur Institute, Cenci Bolognetti Foundation, Rome, Italy.
  • Luquin-Piudo MR; Institute of Molecular Biology and Pathology, CNR, Rome, Italy.
  • Verdier JM; Institute of Neurosciences of Montpellier, INSERM, University of Montpellier, Montpellier, France.
  • Kremer EJ; Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
JCI Insight ; 3(14)2018 07 26.
Article en En | MEDLINE | ID: mdl-30046008
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among the elderly. To understand its pathogenesis and to test therapies, animal models that faithfully reproduce key pathological PD hallmarks are needed. As a prelude to developing a model of PD, we tested the tropism, efficacy, biodistribution, and transcriptional effect of canine adenovirus type 2 (CAV-2) vectors in the brain of Microcebus murinus, a nonhuman primate that naturally develops neurodegenerative lesions. We show that introducing helper-dependent (HD) CAV-2 vectors results in long-term, neuron-specific expression at the injection site and in afferent nuclei. Although HD CAV-2 vector injection induced a modest transcriptional response, no significant adaptive immune response was generated. We then generated and tested HD CAV-2 vectors expressing leucine-rich repeat kinase 2 (LRRK2) and LRRK2 carrying a G2019S mutation (LRRK2G2019S), which is linked to sporadic and familial autosomal dominant forms of PD. We show that HD-LRRK2G2019S expression induced parkinsonian-like motor symptoms and histological features in less than 4 months.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina Límite: Animals Idioma: En Revista: JCI Insight Año: 2018 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina Límite: Animals Idioma: En Revista: JCI Insight Año: 2018 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos