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How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson disease?

Volpicelli-Daley, Laura A; Kirik, Deniz LU ; Stoyka, Lindsay E; Standaert, David G and Harms, Ashley S (2016) In Journal of Neurochemistry 139(S1). p.131-155
Abstract

Animal models of Parkinson disease (PD) are important for understanding the mechanisms of the disease and can contribute to developing and validating novel therapeutics. Ideally, these models should replicate the cardinal features of PD, such as progressive neurodegeneration of catecholaminergic neurons and motor defects. Many current PD models emphasize pathological forms of α-synuclein, based on findings that autosomal dominant mutations in α-synuclein, and duplications/triplications of the SNCA gene cause PD. In addition, Lewy Bodies and Lewy Neurites, primarily composed of α-synuclein, represent the predominant pathological characteristics of PD. These inclusions have defined features such as insolubility in nonionic detergent,... (More)

Animal models of Parkinson disease (PD) are important for understanding the mechanisms of the disease and can contribute to developing and validating novel therapeutics. Ideally, these models should replicate the cardinal features of PD, such as progressive neurodegeneration of catecholaminergic neurons and motor defects. Many current PD models emphasize pathological forms of α-synuclein, based on findings that autosomal dominant mutations in α-synuclein, and duplications/triplications of the SNCA gene cause PD. In addition, Lewy Bodies and Lewy Neurites, primarily composed of α-synuclein, represent the predominant pathological characteristics of PD. These inclusions have defined features such as insolubility in nonionic detergent, hyperphosphorylation, proteinase K sensitivity, a filamentous appearance by electron microscopy and β-sheet structure. Furthermore, it has become clear that Lewy bodies and Lewy neurites are found throughout the peripheral and central nervous system, and could account not only for motor symptoms, but also non-motor symptoms of the disease. The goal of this review is to describe two new α-synuclein based models: the rAAV-α-synuclein model and the α-synuclein fibril model. An advantage of both models is that they do not require extensive cross-breeding of rodents transgenic for α-synuclein with other rodents transgenic for genes of interest to study the impact of such genes on PD-related pathology and phenotypes. In addition, abnormal α-synuclein can be expressed in brain regions relevant for disease. Here, we discuss the features of each model, how each model has contributed thus far to our understanding of PD, and the advantages and potential caveats of each model. This article is protected by copyright. All rights reserved.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurochemistry
volume
139
issue
S1
pages
25 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:84964978411
ISSN
1471-4159
DOI
10.1111/jnc.13627
language
English
LU publication?
yes
id
d9684f31-d3e2-4ed7-966d-aae4aa242d07
date added to LUP
2016-04-18 13:06:11
date last changed
2016-11-20 04:32:37
@misc{d9684f31-d3e2-4ed7-966d-aae4aa242d07,
  abstract     = {<p>Animal models of Parkinson disease (PD) are important for understanding the mechanisms of the disease and can contribute to developing and validating novel therapeutics. Ideally, these models should replicate the cardinal features of PD, such as progressive neurodegeneration of catecholaminergic neurons and motor defects. Many current PD models emphasize pathological forms of α-synuclein, based on findings that autosomal dominant mutations in α-synuclein, and duplications/triplications of the SNCA gene cause PD. In addition, Lewy Bodies and Lewy Neurites, primarily composed of α-synuclein, represent the predominant pathological characteristics of PD. These inclusions have defined features such as insolubility in nonionic detergent, hyperphosphorylation, proteinase K sensitivity, a filamentous appearance by electron microscopy and β-sheet structure. Furthermore, it has become clear that Lewy bodies and Lewy neurites are found throughout the peripheral and central nervous system, and could account not only for motor symptoms, but also non-motor symptoms of the disease. The goal of this review is to describe two new α-synuclein based models: the rAAV-α-synuclein model and the α-synuclein fibril model. An advantage of both models is that they do not require extensive cross-breeding of rodents transgenic for α-synuclein with other rodents transgenic for genes of interest to study the impact of such genes on PD-related pathology and phenotypes. In addition, abnormal α-synuclein can be expressed in brain regions relevant for disease. Here, we discuss the features of each model, how each model has contributed thus far to our understanding of PD, and the advantages and potential caveats of each model. This article is protected by copyright. All rights reserved.</p>},
  author       = {Volpicelli-Daley, Laura A and Kirik, Deniz and Stoyka, Lindsay E and Standaert, David G and Harms, Ashley S},
  issn         = {1471-4159},
  language     = {eng},
  month        = {03},
  number       = {S1},
  pages        = {131--155},
  publisher    = {ARRAY(0x93cc6a8)},
  series       = {Journal of Neurochemistry},
  title        = {How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson disease?},
  url          = {http://dx.doi.org/10.1111/jnc.13627},
  volume       = {139},
  year         = {2016},
}