title: Modeling CNS neurodegeneration by overexpression of disease-causing proteins using viral vectors.
abstract: Defective handling of proteins is a central feature of major neurodegenerative diseases. The discovery that neuronal dysfunction or degeneration can be caused by mutations in single cellular proteins has given new opportunities to model the underlying disease processes by genetic modification of cells in vitro or by generation of transgenic animals carrying the disease-causing gene. Recent developments in recombinant viral-vector technology have opened up an interesting alternative possibility, based on direct gene transfer to selected subregions or subsets of neurons in the brain. Using the highly efficient adeno-associated virus or lentivirus vectors, recent reports have shown that overexpression of mutated human huntingtin or alpha-synuclein in neurons in the striatum or substantia nigra induces progressive neuropathology and neurodegeneration, similar to that seen in Huntington's and Parkinson's diseases. Targeted overexpression of disease-causing genes by recombinant viral vectors provides a new and highly flexible approach for in vivo modeling of neurodegenerative diseases, not only in mice and rats but also in primates.
authors.affiliation: Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, BMC A11, 22184 Lund, Sweden. deniz.kirik@mphy.lu.se
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002490:Central Nervous System / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D000229:Dependovirus; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus; D009154:Mutation; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051843:Synucleins; D051844:alpha-Synuclein