The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease
Abstract
1. Introduction
2. Drosophila melanogaster as Animal Model to Study Human Diseases
3. Drosophila melanogaster as Animal Model for Parkinson’s Disease
4. The Mitochondrial-PD Connection in Drosophila melanogaster
4.1. The Pink1-Parkin Pathway
4.1.1. Mitochondrial Fusion and Fission
4.1.2. Mitophagy
4.1.3. Mitochondrial Complex I
4.2. Parkin-Specific Functions
4.3. The Role of Oxidative Stress in PD
5. Endo-Lysosomal PD Connection in Drosophila melanogaster
5.1. Vesicle Trafficking Endocytosis
5.2. The Retromer Complex
5.3. The Autolysosome
6. Lipids as Connecting Factor between Mitochondrial Dysfunction and a Defective Endo-Lysosomal Pathway in Drosophila melanogaster
6.1. Glucorerebrosidase
6.2. Identification of Underlying Mechanisms in Non-Motor Symptoms in PD
7. Validation in a Mammalian System
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Feature | Limitation | Advantage |
---|---|---|
Life cycle of ~10 days | Too short to study late-life stage signs | A lot of flies in a short amount of time |
Behavior | Not all aspects can be analyzed | Locomotion, sleep, circadian rhythm, can be analyzed |
Brain | Neuronal circuitry is not evolutionarily conserved | Complex neuronal circuitry (including dopaminergic neurons) |
UAS-gal4 system | Off-target effects Overexpression not controlled: too much protein, and thus less physiological condition | Overexpression of human disease genes Knockdown of genes to mimic a loss of function |
Genome | Only 4 chromosomes versus 23 in human | 75% of the disease-causing genes have a fly ortholog |
Human Gene | Drosophila Gene | Disease-Causing OE | LOF | KD | DA Neuron Loss | Motor Deficits | Non-Motor Symptoms | Mito Dysfunction | Endo-Lysosomal Pathway | Lipid Homeostasis | Key Findings in Drosophila |
---|---|---|---|---|---|---|---|---|---|---|---|
SNCA (AD) | / | x | / | / | + | + | + | + | + | + | - link to retromer and sphingolipids |
Parkin (AR) | parkin | x | x | +/− | + | + | + | - functions in the same pathway with Pink1-circadian rhythm - age-dependent mitophagy | |||
PINK1 (AR) | pink1 | x | x | +/− | + | + | + | + | - functions in the same pathway with Parkin - circadian rhythm - age-dependent mitophagy - complex I dysfunction - lipid alterations | ||
DJ-1 (AR) | dj-1α dj-1β | x | x | + | + | ||||||
LRRK2 (AD) | Lrrk | x | x | x | + | + | + | - link to Rab proteins-link to autophagy | |||
VPS35 (AD) | Vps35 | x | x | x | + | + | + | + | - recycling of sphingolipids | ||
Risk genes | |||||||||||
GBA | Gba1a Gba1b | x | x | x | + | + | + | + |
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Vos, M.; Klein, C. The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease. Cells 2021, 10, 579. https://doi.org/10.3390/cells10030579
Vos M, Klein C. The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease. Cells. 2021; 10(3):579. https://doi.org/10.3390/cells10030579
Chicago/Turabian StyleVos, Melissa, and Christine Klein. 2021. "The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease" Cells 10, no. 3: 579. https://doi.org/10.3390/cells10030579
APA StyleVos, M., & Klein, C. (2021). The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease. Cells, 10(3), 579. https://doi.org/10.3390/cells10030579