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Drosophila: A Model System for Human Disease Research
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Drosophila: A Model System for Human Disease Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4715

Special Issue Editor

Dr. Daniela Grifoni

E-Mail Website
Guest Editor
Dipartimento di Medicina Clinica, Sanità Pubblica, Scienze della Vita e dell’Ambiente, Università Dell’Aquila, 67100 L’Aquila, Italy
Interests: cancer genetics; MYC-mediated cell competition; model tumourigenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The fruit fly Drosophila melanogaster has been proven to be a golden model for basic biological research. Over the years, its potential as a tool for deciphering the molecular networks at the basis of human disease has become more and more acknowledged. Uninterrupted efforts of the Drosophila research community have been dedicated to developing new genetic systems aimed at investigating organ, tissue and cellular processes with an increasing level of precision. As a result, the fruit fly now serves as a model not only for basic genetic research, but also for an extraordinarily diverse series of human diseases, from cancer to neurodegeneration and from developmental disorders to drug discovery. As cellular and molecular mechanisms governing organogenesis have been shown to be highly conserved between Drosophila and humans, and given that the fruit fly has functional homologues of most parts of human disease genes, we anticipate that this aspect of Drosophila research will definitely expand in the future.

We invite investigators to contribute original research articles, as well as review articles and opinion papers, that address genetic and molecular mechanisms involved in human disease using the Drosophila model.

Dr. Daniela Grifoni
Guest Editor

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Keywords

  • developmental disease

  • metabolic disease
  • organ disease
  • stem cells and regenerative medicine
  • cancer models
  • neurodegeneration
  • drug discovery and screening

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Published Papers (3 papers)

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Research

20 pages, 4068 KiB  
Article
Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements on Life Span in y w Male Drosophila melanogaster
by Aaron A. Bearden, Emily M. Stewart, Candace C. Casher, Meredith A. Shaddix, Amber C. Nobles and Robin J. Mockett
Int. J. Mol. Sci. 2024, 25(21), 11504; https://doi.org/10.3390/ijms252111504 - 26 Oct 2024
Viewed by 965
Abstract
Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of [...] Read more.
Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or, in a few cases, beginning in middle or late adult life, with concentrations spanning 4–6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1–2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg laying) or fertility (development of progeny to adulthood), but equivalent high doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-Hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila and that further extension of life is difficult in comparatively long-lived flies. Full article
(This article belongs to the Special Issue Drosophila: A Model System for Human Disease Research)
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20 pages, 5918 KiB  
Article
Kismet/CHD7/CHD8 and Amyloid Precursor Protein-like Regulate Synaptic Levels of Rab11 at the Drosophila Neuromuscular Junction
by Emily L. Hendricks, Nicole Linskey, Ireland R. Smith and Faith L. W. Liebl
Int. J. Mol. Sci. 2024, 25(15), 8429; https://doi.org/10.3390/ijms25158429 - 1 Aug 2024
Viewed by 1110
Abstract
The transmembrane protein β-amyloid precursor protein (APP) is central to the pathophysiology of Alzheimer’s disease (AD). The β-amyloid hypothesis posits that aberrant processing of APP forms neurotoxic β-amyloid aggregates, which lead to the cognitive impairments observed in AD. Although numerous additional factors contribute [...] Read more.
The transmembrane protein β-amyloid precursor protein (APP) is central to the pathophysiology of Alzheimer’s disease (AD). The β-amyloid hypothesis posits that aberrant processing of APP forms neurotoxic β-amyloid aggregates, which lead to the cognitive impairments observed in AD. Although numerous additional factors contribute to AD, there is a need to better understand the synaptic function of APP. We have found that Drosophila APP-like (APPL) has both shared and non-shared roles at the synapse with Kismet (Kis), a chromatin helicase binding domain (CHD) protein. Kis is the homolog of CHD7 and CHD8, both of which are implicated in neurodevelopmental disorders including CHARGE Syndrome and autism spectrum disorders, respectively. Loss of function mutations in kis and animals expressing human APP and BACE in their central nervous system show reductions in the glutamate receptor subunit, GluRIIC, the GTPase Rab11, and the bone morphogenetic protein (BMP), pMad, at the Drosophila larval neuromuscular junction (NMJ). Similarly, processes like endocytosis, larval locomotion, and neurotransmission are deficient in these animals. Our pharmacological and epistasis experiments indicate that there is a functional relationship between Kis and APPL, but Kis does not regulate appl expression at the larval NMJ. Instead, Kis likely influences the synaptic localization of APPL, possibly by promoting rab11 transcription. These data identify a potential mechanistic connection between chromatin remodeling proteins and aberrant synaptic function in AD. Full article
(This article belongs to the Special Issue Drosophila: A Model System for Human Disease Research)
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20 pages, 3297 KiB  
Article
Dietary Curcumin Intake and Its Effects on the Transcriptome and Metabolome of Drosophila melanogaster
by Samantha Belcher, Gerardo Flores-Iga, Purushothaman Natarajan, Garrett Crummett, Alicia Talavera-Caro, Celeste Gracia-Rodriguez, Carlos Lopez-Ortiz, Amartya Das, Donald A. Adjeroh, Padma Nimmakayala, Nagamani Balagurusamy and Umesh K. Reddy
Int. J. Mol. Sci. 2024, 25(12), 6559; https://doi.org/10.3390/ijms25126559 - 14 Jun 2024
Viewed by 2029
Abstract
Curcumin, a polyphenol derived from Curcuma longa, used as a dietary spice, has garnered attention for its therapeutic potential, including antioxidant, anti-inflammatory, and antimicrobial properties. Despite its known benefits, the precise mechanisms underlying curcumin’s effects on consumers remain unclear. To address this [...] Read more.
Curcumin, a polyphenol derived from Curcuma longa, used as a dietary spice, has garnered attention for its therapeutic potential, including antioxidant, anti-inflammatory, and antimicrobial properties. Despite its known benefits, the precise mechanisms underlying curcumin’s effects on consumers remain unclear. To address this gap, we employed the genetic model Drosophila melanogaster and leveraged two omics tools—transcriptomics and metabolomics. Our investigation revealed alterations in 1043 genes and 73 metabolites upon supplementing curcumin into the diet. Notably, we observed genetic modulation in pathways related to antioxidants, carbohydrates, and lipids, as well as genes associated with gustatory perception and reproductive processes. Metabolites implicated in carbohydrate metabolism, amino acid biosynthesis, and biomarkers linked to the prevention of neurodegenerative diseases such as schizophrenia, Alzheimer’s, and aging were also identified. The study highlighted a strong correlation between the curcumin diet, antioxidant mechanisms, and amino acid metabolism. Conversely, a lower correlation was observed between carbohydrate metabolism and cholesterol biosynthesis. This research highlights the impact of curcumin on the diet, influencing perception, fertility, and molecular wellness. Furthermore, it directs future studies toward a more focused exploration of the specific effects of curcumin consumption. Full article
(This article belongs to the Special Issue Drosophila: A Model System for Human Disease Research)
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