Format

Send to

Choose Destination
J Parkinsons Dis. 2018;8(2):303-322. doi: 10.3233/JPD-171248.

Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson's Disease in Rodents.

Author information

1
The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
2
Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA.
3
Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA.
4
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
5
Institute for Biocomputation and Complex Systems Physics (BIFI), University of Zaragoza, Zaragoza, Spain.
6
Proteos, Inc, Kalamazoo, MI, USA.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD. This model involves the conversion of recombinant monomeric aSyn protein to a fibrillar form-the aSyn pre-formed fibril (aSyn PFF)-which is then injected into the brain or introduced to the media in culture. Although many groups have successfully adopted and replicated the aSyn PFF model, issues with generating consistent pathology have been reported by investigators. To improve the replicability of this model and diminish these issues, The Michael J. Fox Foundation for Parkinson's Research (MJFF) has enlisted the help of field leaders who performed key experiments to establish the aSyn PFF model to provide the research community with guidelines and practical tips for improving the robustness and success of this model. Specifically, we identify key pitfalls and suggestions for avoiding these mistakes as they relate to generating the aSyn PFFs from monomeric protein, validating the formation of pathogenic aSyn PFFs, and using the aSyn PFFs in vivo or in vitro to model PD. With this additional information, adoption and use of the aSyn PFF model should present fewer challenges, resulting in a robust and widely available model of PD.

KEYWORDS:

Alpha-synuclein; Parkinson’s disease; pre-formed fibril; preclinical model

Supplemental Content

Full text links

Icon for IOS Press Icon for PubMed Central
Loading ...
Support Center