Use of viral vectors to create animal models for Parkinson's disease.
Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While sporadic in the majority of cases, PD-linked dominant mutations in the α-synuclein and LRRK-2 genes, and recessive mutations in the parkin, DJ-1 and PINK-1 genes have been identified in PD families in recent years. In this review we describe viral animal models for PD, i.e. models that are based on PD-associated mutations, and have been generated by viral delivery of the respective disease genes to the substantia nigra of rodents and non-human primates. To date, viral PD models comprise α-synuclein and LRRK-2-based overexpression models, as well as models that mimic parkin loss of function by overexpression of the parkin substrates Pael-R, CDCrel-1, p38/JTV or synphilin-1. These viral models provide valuable insights into Parkinson disease mechanisms, help to identify therapeutic targets and may contribute to the development of therapeutic approaches.
Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
Karin
K
Löw
Patrick
P
Aebischer
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009419:Nerve Tissue Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D058112:Septins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D014780:Viruses / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C480827:GPR37 receptor, human; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C118958:SNCAIP protein, human; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C109366:SEPTIN5 protein, human; D058112:Septins