Calcium-independent Phospholipase A2β is Vital in Neurons and Possibly Other Tissues to Inhibit Age-Related Motor Degeneration.
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Senior honors thesis -- Open Access per signed student consent form
By 2020, nearly one million Americans will be living with Parkinson’s disease (PD), and nearly ten million worldwide. This number outstrips every other age-related neurodegenerative disease save for Alzheimer disease (AD). The underlying cause of PD remains elusive, as does a medical remedy. Several genes have been linked to the disease, such as PLA2G6 (also known as iPLA2, PARK14, and iPLA2-VIA), a calcium-independent phospholipase A2 (iPLA2), which has been implicated in two forms of PD: Dystonia-parkinsonism (DP) and autosomal recessive early-onset parkinsonism (AREP). PLA2G6 has also been associated with Infantile neuroaxonal dystrophy (INAD) and atypical neuroaxonal dystrophy (aNAD). The model organism Drosophila melanogaster contains one homolog for PLA2G6. Previous studies have established knockout PLA2G6 Drosophila mutants showing locomotor defects, decreased lifespan, and increased sensitivity to oxidative stress − all symptoms of PD and other PLA2G6-associated neurodegeneration (PLAN) diseases. To better understand the mechanism and cell types by which PLA2G6 works, I used the GAL4-UAS and RNAi systems to generate two fly lines: one with PLA2G6 knockdown in neuronal tissue and one with ubiquitous knockdown. I found that the while PLA2G6 was required for neuronal upkeep to prevent age-related locomotor decline, neuronal tissue alone does not explain the full extent of the disease pathology. Based on these findings, a more universal approach should be taken when dealing with PLA2G6 related diseases. I believe that this information will be insightful and useful for future therapeutic approaches combating PLAN diseases.
Shulman, Benjamin. (September 2019). Calcium-independent Phospholipase A2β is Vital in Neurons and Possibly Other Tissues to Inhibit Age-Related Motor Degeneration. Thesis Submitted in Partial Fulfillment of the Requirements of the Jay and Jeanie Schottenstein Honors Program Yeshiva College Yeshiva University.
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