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Viral Vector-Based Models of Parkinson’s Disease

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Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 22))

Abstract

In order to study the molecular pathways of Parkinson’s disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models as an alternative to toxin-based models. Viral vector-mediated loco-regional gene delivery provides an attractive way to express transgenes in the central nervous system. Several vector systems based on various viruses have been developed. In this chapter, we give an overview of the different viral vector systems used for targeting the CNS. Further, we describe the different viral vector-based PD models currently available based on overexpression strategies for autosomal dominant genes such as α-synuclein and LRRK2, and knockout or knockdown strategies for autosomal recessive genes, such as parkin, DJ-1, and PINK1. Models based on overexpression of α-synuclein are the most prevalent and extensively studied, and therefore the main focus of this chapter. Many efforts have been made to increase the expression levels of α-synuclein in the dopaminergic neurons. The best α-synuclein models currently available have been developed from a combined approach using newer AAV serotypes and optimized vector constructs, production, and purification methods. These third-generation α-synuclein models show improved face and predictive validity, and therefore offer the possibility to reliably test novel therapeutics.

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  1. Katholieke Universiteit Leuven, Leuven, Belgium

    Anke Van der Perren, Chris Van den Haute & Veerle Baekelandt

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  1. Anke Van der Perren
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Correspondence to Anke Van der Perren .

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  1. Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany

    Hoa Huu Phuc Nguyen

  2. Dept of Experimental Medical Science, Lund University, Lund, Sweden

    M. Angela Cenci

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Van der Perren, A., Van den Haute, C., Baekelandt, V. (2014). Viral Vector-Based Models of Parkinson’s Disease. In: Nguyen, H., Cenci, M. (eds) Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease. Current Topics in Behavioral Neurosciences, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2014_310

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