Understanding Pathophysiology of Sporadic Parkinson's Disease in Drosophila Model: Potential Opportunities and Notable Limitations

Abstract

Parkinson s disease PD is the second most common neurodegenerative disorder affecting approximately % of the population over age . PD is widely accepted as a multifactorial disease with both genetic and environmental contributions. Despite extensive research conducted in the area the precise etiological factors responsible remain elusive. In about % Parkinsonism is considered to have a sporadic component. There are currently no established curative, preventative, or diseasemodifying interventions, stemming from a poor understanding of the molecular mechanisms of pathogenesis. Here lies the importance of animal models. Pharmacological insults cause Parkinsonian like phenotypes in Drosophila, thereby modelling sporadic PD. The pesticides paraquat and rotenone induced oxidative damage causing cluster specific D" neuron loss together with motor deficits. Studies in fly PD model have deciphered that signaling pathways such as phosphatidylinositolkinase PI K/"kt and target of rapamycin TOR , c-Jun N-terminal kinase JNK have been defective. Further, these studies have demonstrated that fruit fly can be a potential model to screen chemical compounds for their neuroprotective efficacy. This chapter overviews current knowledge on the pathophysiology of sporadic PD employing Drosophila model and discusses the future perspectives. Further we emphasize the importance of performing genome wide screens in fly model, which

Drosophila<em> melanogaster</em> as a Translational Model System to Explore the Impact of Phytochemicals on Human Health

“…Similarly, studies have shown that plant-derived molecules can be effective in treating Parkinson's disease (PD), which is characterized by the formation of Lewy bodies containing alpha-synuclein and the loss of dopaminergic neurons resulting in motor symptoms [114]. Gardenine-A, a phytochemical derived from the plant Gardenia resinifera, has been found to have neuroprotective effects in Drosophila models of PD by reducing mortality and modulating inflammatory and cellular responses [115].…”

Sexual dysfunction precedes motor defects, dopaminergic neuronal degeneration, and impaired dopamine metabolism: Insights from Drosophila model of Parkinson’s disease

“…Parkinson’s disease (PD) is the second most dominant neurodegenerative disorder that affects about 1% of the population over age 50 ( Modi et al, 2016 ). Sexual dysfunction (SD) is one of the most common non-motor disorders affecting Parkinsonian patients and remains the most neglected, underreported, and underrecognized aspect of PD ( Jitkritsadakul et al, 2015 ; Bhattacharyya and Rosa-Grilo, 2017 ; Vela-Desojo et al, 2020 ; Benigno et al, 2022 ; Bronner et al, 2022 ; Elshamy et al, 2022 ).…”

Leukotriene Signaling as a Target in α-Synucleinopathies

“…Although the vast majority of cases occur sporadically and different environmental factors, such as exposure to herbicides/pesticides or heavy metals, strongly influence the susceptibility to developing α-synucleinopathies, several genetic risk variants have been identified. Some of these risk genes are shared between PD and DLB, as well as between familial and sporadic forms of the diseases [6][7][8][9][10] (Figure 1). Not only SNCA, which is the gene encoding for α-syn, but also GBA encoding β-glucocerebrosidase (GCase) is a mutual genetic risk factor of PD and DLB [6,11].…”