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The AAV-α-Synuclein Model of Parkinson's Disease : An Update

Björklund, Anders LU orcid and Mattsson, Bengt LU (2024) In Journal of Parkinson's Disease
Abstract

Targeted delivery of α-synuclein using AAV vectors has over the two decades since its introduction developed into a versatile tool for modeling different aspects of synucleinopathy, mimicking those seen in Parkinson's disease and related Lewy body disorders. The viral vector approach to disease modeling is attractive in that the expression of α-synuclein, wild-type or mutated, can be confined to defined anatomical structures and targeted to selected cell populations using either cell-type specific promoter constructs or different natural or engineered AAV serotypes. AAV-α-synuclein was initially used to model progressive α-synuclein pathology in nigral dopamine neurons, and, like the standard 6-OHDA model, it has most commonly been... (More)

Targeted delivery of α-synuclein using AAV vectors has over the two decades since its introduction developed into a versatile tool for modeling different aspects of synucleinopathy, mimicking those seen in Parkinson's disease and related Lewy body disorders. The viral vector approach to disease modeling is attractive in that the expression of α-synuclein, wild-type or mutated, can be confined to defined anatomical structures and targeted to selected cell populations using either cell-type specific promoter constructs or different natural or engineered AAV serotypes. AAV-α-synuclein was initially used to model progressive α-synuclein pathology in nigral dopamine neurons, and, like the standard 6-OHDA model, it has most commonly been applied unilaterally, using the non-injected side as a reference and control. In recent years, however, the AAV-α-synuclein model has become more widely used to induce Parkinson-like synuclein pathology in other relevant neuronal systems, such as the brainstem noradrenergic and serotonergic neurons, the vagal motor neurons, as well as in oligodendrocytes, the prime target relevant to the pathology seen in multiple system atrophy. The purpose of this review is to give an overview of the progress made in the use of the AAV-α-synuclein model over the last two decades and summarize the state-of-the art in the use of the AAV-α-synuclein model for disease modeling in rats and mice.

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Contribution to journal
publication status
epub
subject
in
Journal of Parkinson's Disease
publisher
IOS Press
external identifiers
  • pmid:39031386
ISSN
1877-718X
DOI
10.3233/JPD-240207
language
English
LU publication?
yes
id
d21d7712-cf05-46e7-9e08-40632f7575b9
date added to LUP
2024-08-06 08:31:32
date last changed
2024-08-06 08:50:48
@article{d21d7712-cf05-46e7-9e08-40632f7575b9,
  abstract     = {{<p>Targeted delivery of α-synuclein using AAV vectors has over the two decades since its introduction developed into a versatile tool for modeling different aspects of synucleinopathy, mimicking those seen in Parkinson's disease and related Lewy body disorders. The viral vector approach to disease modeling is attractive in that the expression of α-synuclein, wild-type or mutated, can be confined to defined anatomical structures and targeted to selected cell populations using either cell-type specific promoter constructs or different natural or engineered AAV serotypes. AAV-α-synuclein was initially used to model progressive α-synuclein pathology in nigral dopamine neurons, and, like the standard 6-OHDA model, it has most commonly been applied unilaterally, using the non-injected side as a reference and control. In recent years, however, the AAV-α-synuclein model has become more widely used to induce Parkinson-like synuclein pathology in other relevant neuronal systems, such as the brainstem noradrenergic and serotonergic neurons, the vagal motor neurons, as well as in oligodendrocytes, the prime target relevant to the pathology seen in multiple system atrophy. The purpose of this review is to give an overview of the progress made in the use of the AAV-α-synuclein model over the last two decades and summarize the state-of-the art in the use of the AAV-α-synuclein model for disease modeling in rats and mice.</p>}},
  author       = {{Björklund, Anders and Mattsson, Bengt}},
  issn         = {{1877-718X}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{IOS Press}},
  series       = {{Journal of Parkinson's Disease}},
  title        = {{The AAV-α-Synuclein Model of Parkinson's Disease : An Update}},
  url          = {{https://lup.lub.lu.se/search/files/192555576/publication_in_Journal_of_Parkinson_s_Disease.pdf}},
  doi          = {{10.3233/JPD-240207}},
  year         = {{2024}},
}