Imagine you’re organizing a marathon race, but some of the runners start to stumble and fall along the way. You discover that their muscles are weak, and their joints are stiff. This is similar to what happens in Parkinson’s Disease (PD), where certain neurons in the brain degenerate, leading to movement problems. Scientists have been studying PD to find effective treatments, but it remains a challenge. One aspect they’re focusing on is the role of mitochondria, which are like the powerhouses of our cells. In PD, mitochondrial dysfunction seems to play a significant role. Researchers have discovered a process called mitophagy, which is like a garbage disposal system for damaged mitochondria. By enhancing mitophagy, they hope to clear out malfunctioning mitochondria and potentially improve PD symptoms. Using fruit fly models called Drosophila melanogaster, scientists are exploring how mitophagy modulators could be used as therapeutic strategies for PD. This research could pave the way for new drugs or compounds that target mitophagy and offer hope for people living with PD.

Parkinson’s disease (PD) is the second most popular age-associated neurodegenerative disorder after Alzheimer’s disease. The degeneration of dopaminergic neurons, aggregation of α-synuclein (α-syn), and locomotor defects are the main characteristic features of PD. The main cause of a familial form of PD is associated with a mutation in genes such as SNCA, PINK1, Parkin, DJ-1, LRKK2, and others. Recent advances have uncovered the different underlying mechanisms of PD but the treatment of PD is still unknown due to the unavailability of effective therapies and preventive medicines in the current scenario. The pathophysiology and genetics of PD have been strongly associated with mitochondria in disease etiology. Several studies have investigated a complex molecular mechanism governing the identification and clearance of dysfunctional mitochondria from the cell, a mitochondrial quality control mechanism called mitophagy. Reduced mitophagy and mitochondrial impairment are found in both sporadic and familial PD. Pharmacologically modulating mitophagy and accelerating the removal of defective mitochondria are of common interest in developing a therapy for PD. However, despite the extensive understanding of the mitochondrial quality control pathway and its underlying mechanism, the therapeutic potential of targeting mitophagy modulation and its role in PD remains to be explored. Thus, targeting mitophagy using chemical agents and naturally occurring phytochemicals could be an emerging therapeutic strategy in PD prevention and treatment. We discuss the current research on understanding the role of mitophagy modulators in PD using Drosophila melanogaster as a model. We further explore the contribution of Drosophila in the pathophysiology of PD, and discuss comprehensive genetic analysis in flies and pharmacological drug screening to develop potential therapeutic molecules for PD.

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