In vivo gene delivery for development of mammalian models for Parkinson's disease
Ayse Ulusoy1, Tomas Bjorklund, Stephan Hermening
1CNS Disease Modeling Unit, Section of Neuroscience, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Abstract:
During the last decade, identification of the genes involved in familial forms of Parkinson's disease (PD) has advanced our understanding of the mechanisms underlying the development of different aspects of PD. However the available animal models still remain as the main limiting factor for the development of neuroprotective therapies that can halt the progression of the disease, through which we wish to provide a better quality of life for the PD patients. Here, we review the recently developed animal models based on overexpression of PD-associated genes using recombinant viral vectors. Recombinant adeno-associated viral vectors, in particular, have been very useful in targeting the nigral dopamine neurons both in the rodent and the primate brain. In order to provide insights into the establishment of these models in the laboratory, we will not only give an overview of the results from these studies but also cover practical issues related to the production and handling of the viral vectors, which are critical for the successful application of this approach.
Insights
New animal models using viral vectors help study Parkinson's disease (PD) gene functions. These models advance understanding and aid development of neuroprotective therapies for Parkinson's patients.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Familial Parkinson's disease (PD) gene identification has improved understanding of disease mechanisms.
- Current animal models are insufficient for developing effective neuroprotective therapies for PD.
- Advancing PD research requires better models to test treatments and improve patient quality of life.
Purpose of the Study:
- To review recently developed animal models for Parkinson's disease (PD).
- To focus on models utilizing overexpression of PD-associated genes via recombinant viral vectors.
- To provide insights into establishing and utilizing these advanced PD models in research settings.
Main Methods:
- Review of studies employing recombinant viral vectors, particularly adeno-associated viral vectors (AAV).
- Analysis of AAV vector applications for targeting nigral dopamine neurons in rodent and primate brains.
- Discussion of practical aspects of viral vector production and handling for model creation.
Main Results:
- Recombinant adeno-associated viral vectors are effective tools for genetic manipulation in PD research.
- These viral vector-based models allow for targeted gene overexpression in specific neuronal populations.
- Successful application of these models has been demonstrated in both rodent and primate studies.
Conclusions:
- Viral vector-mediated gene delivery offers a promising approach for creating advanced animal models of Parkinson's disease.
- These models are crucial for dissecting PD pathogenesis and evaluating novel neuroprotective strategies.
- Further development and application of these models will accelerate the search for effective PD treatments.
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