| |
| author |
Evan Fairweather
| | title |
Developing a LRRK2 Model of Parkinson's Disease in C. elegans
| | abstract |
Parkinson's disease (PD) is the second most common neurodegenerative disorder
worldwide. PD has a multifactorial etiology, with genetic, environmental, and lifestyle factors
identified by epidemiological studies. One such genetic factor is mutation of the leucine-rich-
repeat-kinase-2 gene (LRRK2), responsible for up to 40% of familial PD in certain populations.
While treatment options such as pharmacological dopamine supplementation with L-DOPA are
available, they do not address the underlying molecular mechanisms of disease. As such, the
identification of targeted therapeutic compounds stands to significantly reduce the morbidity of
Parkinson's disease. The development of a model system using the nematode C. elegans is the
first step in such a process. With a simple, well characterized nervous system with significant
biochemical similarity to that of humans, they have demonstrated considerable utility in
modeling the mechanisms of human neurological disease. This study sought to develop a robust
behavioral assay capable of quantifying C. elegans motor deficits, as well as correlate such
deficits with the degeneration of cephalic dopaminergic neurons. Such a model system could
then be employed in the screening of novel therapeutics, such as kinase inhibitors for the
treatment of LRRK2-PD. It was found that the basal slowing assay, which measures the change
in locomotor rate in the presence and absence of a bacterial lawn, may have potential for such
purposes. As hypothesized, wildtype worms exhibited an intact basal slowing response, whereas
dopamine deficient transgenic worms exhibited a phenotype consistent with the loss of this
dopaminergic behavior. However, observations of LRRK2 mutant C. elegans were inconsistent
with expectations, wherein no time-dependent loss of the basal slowing response was observed
despite gradual degeneration of their dopaminergic neurons. Further study is needed to evaluate
the utility and practicality of this assay in the development of a robust PD model system.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.S. (2022)
|
| advisor |
Marvin Bayne
|
| full text | EFairweather.pdf |
| |
