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Viral vector-mediated overexpression of α-synuclein as a progressive model of Parkinson's disease

Ulusoy, Ayse LU ; Decressac, Mickael LU ; Kirik, Deniz LU and Björklund, Anders LU (2010) In Progress in Brain Research 184. p.89-111
Abstract

The discovery of the role of α-synuclein in the pathogenesis of Parkinson's disease (PD) has opened new possibilities for the development of more authentic models of Parkinson's disease. Recombinant adeno-associated virus (AAV) and lentivirus (LV) vectors are efficient tools for expression of genes locally in subsets of neurons in the brain and can be used to express human wild-type or mutated α-synuclein selectively in midbrain dopamine neurons. Using this approach, it is possible to trigger extensive PD-like cellular and axonal pathologies in the nigrostriatal projection, involving abnormal protein aggregation, neuronal dysfunction, and cell death that develop progressively over time. Targeted overexpression of human α-synuclein in... (More)

The discovery of the role of α-synuclein in the pathogenesis of Parkinson's disease (PD) has opened new possibilities for the development of more authentic models of Parkinson's disease. Recombinant adeno-associated virus (AAV) and lentivirus (LV) vectors are efficient tools for expression of genes locally in subsets of neurons in the brain and can be used to express human wild-type or mutated α-synuclein selectively in midbrain dopamine neurons. Using this approach, it is possible to trigger extensive PD-like cellular and axonal pathologies in the nigrostriatal projection, involving abnormal protein aggregation, neuronal dysfunction, and cell death that develop progressively over time. Targeted overexpression of human α-synuclein in midbrain dopamine neurons, using AAV vectors, reproduces many of the characteristic features of the human disease and provides, for the first time, a model of progressive PD that can be applied to both rodents and primates.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Synuclein, Dopamine, Nigrostriatal system, Motor impairment, Adeno-associated virus, Lentivirus, Viral vectors, Animal models
in
Progress in Brain Research
volume
184
pages
23 pages
publisher
Elsevier
external identifiers
  • wos:000287856300006
  • scopus:77957224859
ISSN
1875-7855
DOI
10.1016/S0079-6123(10)84005-1
language
English
LU publication?
yes
id
084e1107-2d8f-4fce-bb2d-3425f6845593 (old id 1859368)
date added to LUP
2011-04-01 08:15:30
date last changed
2018-06-10 04:21:29
@article{084e1107-2d8f-4fce-bb2d-3425f6845593,
  abstract     = {<p>The discovery of the role of α-synuclein in the pathogenesis of Parkinson's disease (PD) has opened new possibilities for the development of more authentic models of Parkinson's disease. Recombinant adeno-associated virus (AAV) and lentivirus (LV) vectors are efficient tools for expression of genes locally in subsets of neurons in the brain and can be used to express human wild-type or mutated α-synuclein selectively in midbrain dopamine neurons. Using this approach, it is possible to trigger extensive PD-like cellular and axonal pathologies in the nigrostriatal projection, involving abnormal protein aggregation, neuronal dysfunction, and cell death that develop progressively over time. Targeted overexpression of human α-synuclein in midbrain dopamine neurons, using AAV vectors, reproduces many of the characteristic features of the human disease and provides, for the first time, a model of progressive PD that can be applied to both rodents and primates.</p>},
  author       = {Ulusoy, Ayse and Decressac, Mickael and Kirik, Deniz and Björklund, Anders},
  issn         = {1875-7855},
  keyword      = {Synuclein,Dopamine,Nigrostriatal system,Motor impairment,Adeno-associated virus,Lentivirus,Viral vectors,Animal models},
  language     = {eng},
  pages        = {89--111},
  publisher    = {Elsevier},
  series       = {Progress in Brain Research},
  title        = {Viral vector-mediated overexpression of α-synuclein as a progressive model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1016/S0079-6123(10)84005-1},
  volume       = {184},
  year         = {2010},
}