Abstract
Improvements to the diagnosis and treatment of Parkinson disease (PD) are dependent upon the identification and molecular understanding of modifiers of neuronal degeneration. Here, we describe the use of multifactorial functional analyses to exploit the experimental attributes of the nematode, Caenorhabditis elegans, to accelerate the translational path toward identification and characterization of modifiers of dopaminergic neurogeneration. C. elegans is ideal for both screening and target validation of potential modifiers. Specific assays discussed in this technical overview include in vivo analyses using whole, intact, and living nematodes with readouts for age-dependent α-synuclein-proteotoxicity and 6-hydroxydopamine-induced neurodegeneration in dopamine (DA) neurons. These methods provide an integrated approach to target characterization and functional validation in C. elegans that allow researchers to prioritize lead candidates for translation toward mammalian systems.
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Acknowledgements
We would like to thank our collaborators and all members of the Caldwell laboratory for their collegiality and contributions to the research presented here. Special thanks to Adam Harrington for generating the data presented on neuronal RNAi and Michelle Tucci for C. elegans DA neuron images.
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Caldwell, K.A., Caldwell, G.A. (2011). Methodological Strategies to Evaluate Functional Effectors Related to Parkinson’s Disease Through Application of Caenorhabditis elegans Models. In: Lane, E., Dunnett, S. (eds) Animal Models of Movement Disorders. Neuromethods, vol 61. Humana Press. https://doi.org/10.1007/978-1-61779-298-4_3
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DOI: https://doi.org/10.1007/978-1-61779-298-4_3
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