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Special Issue "Role of Drosophila in Human Disease Research"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 August 2020.

Special Issue Editors

Prof. Masamitsu Yamaguchi
Website
Guest Editor
Department of Applied Biology, Kyoto Institute of Technology, Kyoto 606-8585, Japan
Interests: Drosophila model for human disease; epigenetics; DNA replication gene; autism spectrum disorder
Prof. Shinya Yamamoto
Website
Guest Editor
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 United States
Interests: Rare and Undiagnosed Diseases; Drosophila melanogaster ; Notch signaling; Dopamine Signaling

Special Issue Information

Dear Colleagues,

For over a century, Drosophila melanogaster has been widely used in classical and modern genetics. For over a decade, Drosophila has been used as a highly tractable animal model for studying human diseases. Many biological functions, including physical and neurological properties, are highly conserved between humans and Drosophila. Moreover, nearly 75% of human-disease-causing genes have their functional homologues in Drosophila. Drosophila has been successful in the study of various neurodegenerative diseases, metabolic syndromes, and cancer. It is also playing a role in the evaluation of candidate substances for treatment of these human diseases. Currently, scientists are studying more complex psychiatric disorders, aging, and rare intractable human genetic diseases using Drosophila models. However, we always have to keep in mind both the benefits and limitations of fly models by comparing them to other animal models, such as mouse, zebra fish, and nematode worm models. For this Special Issue, we welcome original research articles and up-to-date review articles that provide novel insights into the related academic fields.

Prof. Masamitsu Yamaguchi
Prof. Shinya Yamamoto
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Drosophila melanogaster
  • Human disease model
  • Cancer
  • Neurodegeneration
  • Psychiatric disorder
  • Intellectual disorder
  • Metabolic syndrome
  • Aging
  • Epigenetic dysregulation
  • Mitochondrial disorder
  • Infectious diseases

Published Papers (7 papers)

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Research

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Open AccessArticle
Abnormal Social Interactions in a Drosophila Mutant of an Autism Candidate Gene: Neuroligin 3
Int. J. Mol. Sci. 2020, 21(13), 4601; https://doi.org/10.3390/ijms21134601 - 29 Jun 2020
Abstract
Social interactions are typically impaired in neuropsychiatric disorders such as autism, for which the genetic underpinnings are very complex. Social interactions can be modeled by analysis of behaviors, including social spacing, sociability, and aggression, in simpler organisms such as Drosophila melanogaster. Here, [...] Read more.
Social interactions are typically impaired in neuropsychiatric disorders such as autism, for which the genetic underpinnings are very complex. Social interactions can be modeled by analysis of behaviors, including social spacing, sociability, and aggression, in simpler organisms such as Drosophila melanogaster. Here, we examined the effects of mutants of the autism-related gene neuroligin 3 (nlg3) on fly social and non-social behaviors. Startled-induced negative geotaxis is affected by a loss of function nlg3 mutation. Social space and aggression are also altered in a sex- and social-experience-specific manner in nlg3 mutant flies. In light of the conserved roles that neuroligins play in social behavior, our results offer insight into the regulation of social behavior in other organisms, including humans. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Open AccessArticle
Anti-Aging Effect of the Ketone Metabolite β-Hydroxybutyrate in Drosophila Intestinal Stem Cells
Int. J. Mol. Sci. 2020, 21(10), 3497; https://doi.org/10.3390/ijms21103497 - 15 May 2020
Cited by 1
Abstract
Age-related changes in tissue-resident adult stem cells may be closely linked to tissue aging and age-related diseases, such as cancer. β-Hydroxybutyrate is emerging as an important molecule for exhibiting the anti-aging effects of caloric restriction and fasting, which are generally considered to be [...] Read more.
Age-related changes in tissue-resident adult stem cells may be closely linked to tissue aging and age-related diseases, such as cancer. β-Hydroxybutyrate is emerging as an important molecule for exhibiting the anti-aging effects of caloric restriction and fasting, which are generally considered to be beneficial for stem cell maintenance and tissue regeneration. The effects of β-hydroxybutyrate on adult stem cells remain largely unknown. Therefore, this study was undertaken to investigate whether β-hydroxybutyrate supplementation exerts beneficial effects on age-related changes in intestinal stem cells that were derived from the Drosophila midgut. Our results indicate that β-hydroxybutyrate inhibits age- and oxidative stress-induced changes in midgut intestinal stem cells, including centrosome amplification (a hallmark of cancers), hyperproliferation, and DNA damage accumulation. Additionally, β-hydroxybutyrate inhibits age- and oxidative stress-induced heterochromatin instability in enterocytes, an intestinal stem cells niche cells. Our results suggest that β-hydroxybutyrate exerts both intrinsic as well as extrinsic influence in order to maintain stem cell homeostasis. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Open AccessArticle
Loss of Histone Locus Bodies in the Mature Hemocytes of Larval Lymph Gland Result in Hyperplasia of the Tissue in mxc Mutants of Drosophila
Int. J. Mol. Sci. 2020, 21(5), 1586; https://doi.org/10.3390/ijms21051586 - 26 Feb 2020
Abstract
Mutations in the multi sex combs (mxc) gene in Drosophila results in malignant hyperplasia in larval hematopoietic tissues, called lymph glands (LG). mxc encodes a component of the histone locus body (HLB) that is essential for cell cycle-dependent transcription and processing [...] Read more.
Mutations in the multi sex combs (mxc) gene in Drosophila results in malignant hyperplasia in larval hematopoietic tissues, called lymph glands (LG). mxc encodes a component of the histone locus body (HLB) that is essential for cell cycle-dependent transcription and processing of histone mRNAs. The mammalian nuclear protein ataxia-telangiectasia (NPAT) gene, encoded by the responsible gene for ataxia telangiectasia, is a functional Mxc orthologue. However, their roles in tumorigenesis are unclear. Genetic analyses of the mxc mutants and larvae having LG-specific depletion revealed that a reduced activity of the gene resulted in the hyperplasia, which is caused by hyper-proliferation of immature LG cells. The depletion of mxc in mature hemocytes of the LG resulted in the hyperplasia. Furthermore, the inhibition of HLB formation was required for LG hyperplasia. In the mutant larvae, the total mRNA levels of the five canonical histones decreased, and abnormal forms of polyadenylated histone mRNAs, detected rarely in normal larvae, were generated. The ectopic expression of the polyadenylated mRNAs was sufficient for the reproduction of the hyperplasia. The loss of HLB function, especially 3′-end processing of histone mRNAs, is critical for malignant LG hyperplasia in this leukemia model in Drosophila. We propose that mxc is involved in the activation to induce adenosine deaminase-related growth factor A (Adgf-A), which suppresses immature cell proliferation in LG. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Review

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Open AccessReview
Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster
Int. J. Mol. Sci. 2020, 21(13), 4621; https://doi.org/10.3390/ijms21134621 - 29 Jun 2020
Abstract
Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer’s disease (AD). The clinical symptoms of AD include progressive memory loss and [...] Read more.
Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer’s disease (AD). The clinical symptoms of AD include progressive memory loss and impairment of cognitive functions that interfere with daily life activities. The predominant neuropathological features in AD are extracellular β-amyloid (Aβ) plaque deposition and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Because of its complex pathobiology, some tangible treatment can only ameliorate the symptoms, but not prevent the disease altogether. Numerous drugs during pre-clinical or clinical studies have shown no positive effect on the disease outcome. Therefore, understanding the basic pathophysiological mechanism of AD is imperative for the rational design of drugs that can be used to prevent this disease. Drosophila melanogaster has emerged as a highly efficient model system to explore the pathogenesis and treatment of AD. In this review we have summarized recent advancements in the pharmacological research on AD using Drosophila as a model species, discussed feasible treatment strategies and provided further reference for the mechanistic study and treatment of age-related AD. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Open AccessReview
Genetic Dissection of Alzheimer’s Disease Using Drosophila Models
Int. J. Mol. Sci. 2020, 21(3), 884; https://doi.org/10.3390/ijms21030884 - 30 Jan 2020
Cited by 1
Abstract
Alzheimer’s disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid β (Aβ) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains [...] Read more.
Alzheimer’s disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid β (Aβ) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains symptomatic. Molecular understanding of the pathogenesis and progression of AD is necessary to develop disease-modifying treatment. Drosophila, as the most advanced genetic model, has been used to explore the molecular mechanisms of AD in the last few decades. Here, we introduce Drosophila AD models based on human Aβ and summarize the results of their genetic dissection. We also discuss the utility of functional genomics using the Drosophila system in the search for AD-associated molecular mechanisms in the post-genomic era. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Open AccessReview
Drosophila as a Model Organism to Understand the Effects during Development of TFIIH-Related Human Diseases
Int. J. Mol. Sci. 2020, 21(2), 630; https://doi.org/10.3390/ijms21020630 - 17 Jan 2020
Cited by 1
Abstract
Human mutations in the transcription and nucleotide excision repair (NER) factor TFIIH are linked with three human syndromes: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS). In particular, different mutations in the XPB, XPD and p8 subunits of TFIIH may cause one [...] Read more.
Human mutations in the transcription and nucleotide excision repair (NER) factor TFIIH are linked with three human syndromes: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS). In particular, different mutations in the XPB, XPD and p8 subunits of TFIIH may cause one or a combination of these syndromes, and some of these mutations are also related to cancer. The participation of TFIIH in NER and transcription makes it difficult to interpret the different manifestations observed in patients, particularly since some of these phenotypes may be related to problems during development. TFIIH is present in all eukaryotic cells, and its functions in transcription and DNA repair are conserved. Therefore, Drosophila has been a useful model organism for the interpretation of different phenotypes during development as well as the understanding of the dynamics of this complex. Interestingly, phenotypes similar to those observed in humans caused by mutations in the TFIIH subunits are present in mutant flies, allowing the study of TFIIH in different developmental processes. Furthermore, studies performed in Drosophila of mutations in different subunits of TFIIH that have not been linked to any human diseases, probably because they are more deleterious, have revealed its roles in differentiation and cell death. In this review, different achievements made through studies in the fly to understand the functions of TFIIH during development and its relationship with human diseases are analysed and discussed. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Open AccessReview
Autism Spectrum Disorder-Related Syndromes: Modeling with Drosophila and Rodents
Int. J. Mol. Sci. 2019, 20(17), 4071; https://doi.org/10.3390/ijms20174071 - 21 Aug 2019
Cited by 1
Abstract
Whole exome analyses have identified a number of genes associated with autism spectrum disorder (ASD) and ASD-related syndromes. These genes encode key regulators of synaptogenesis, synaptic plasticity, cytoskeleton dynamics, protein synthesis and degradation, chromatin remodeling, transcription, and lipid homeostasis. Furthermore, in silico studies [...] Read more.
Whole exome analyses have identified a number of genes associated with autism spectrum disorder (ASD) and ASD-related syndromes. These genes encode key regulators of synaptogenesis, synaptic plasticity, cytoskeleton dynamics, protein synthesis and degradation, chromatin remodeling, transcription, and lipid homeostasis. Furthermore, in silico studies suggest complex regulatory networks among these genes. Drosophila is a useful genetic model system for studies of ASD and ASD-related syndromes to clarify the in vivo roles of ASD-associated genes and the complex gene regulatory networks operating in the pathogenesis of ASD and ASD-related syndromes. In this review, we discuss what we have learned from studies with vertebrate models, mostly mouse models. We then highlight studies with Drosophila models. We also discuss future developments in the related field. Full article
(This article belongs to the Special Issue Role of Drosophila in Human Disease Research)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Recent advances in Drosophila models for Charcot-Marie-Tooth disease

Authors: Fukiko Kitani-Morii et al

Abstract: Charcot-Marie-Tooth disease (CMT) is the most frequent hereditary peripheral neuropathy in the world. Typical clinical manifestations of CMT are young-onset and slowly progressive distal dominant muscle atrophy and sensory loss. Until now, CMT has no radical treatments. Currently, more than 80 disease-causing genes have been identified and advances in genetic screening are expected to continue discovering new disease-causing genes. Drosophila model of CMT can reproduce the disease phenotype with diverse genetic backgrounds and offer many advantages for CMT research. In this review, we describe the major findings and recent advances on the molecular pathogenesis of axonal CMT and discuss future prospects for the field.

Title: Drosophila model to study the role of glia in human neuronal diseases

Authors: Im-Soon Lee

Abstract: Glial cells are key players for proper formation and maintenance of nervous system, thus contributing to neuronal health and disease in human. However, little is known about the molecular pathways that govern glia-neuron communication in the diseased brain. Drosophila provides a useful in vivo model to explore the conserved molecular details of glial cell biology and their contributions to brain function and disease susceptibility. In this review, we will address recent findings on Drosophila models that explore glial influence on normal neuronal activity and specific glial defects that cause neuronal death.

Title: Mass spectrometry imaging for metabolites imaging in Drosophila melanogaster -A review

Authors: Shuichi Shimma

Abstract: Mass spectrometry imaging (MSI) is a technology that directly detects molecules in a sample by mass spectrometry and visualizes their distribution of various molecules without labeling. Currently, it has been applied to various samples, and molecular imaging results in Drosophila melanogaster (D. melanogaster) using MSI have also been reported. Although there have been few reports on D. melanogaster analysis using MSI, it is expected that a more detailed understanding of the disease state will be possible in the future. For example, a comparison of biomolecular distributions between the disease state model and wild type would provide new insights towards the disease. In this review, the principles of MSI, its application to D. melanogaster, and its future development are described.

Title: Can we make Drosophila model of CADASIL?

Authors: Ikuko Mizuta

Title: Drosophila models of PRPS-associated disorders using CRISPR/Cas9

Authors: Keemo Delos Santos, Eunjeong Kwon, Nam-Sung Moon

Abstract: While a plethora of genetic techniques have been developed over the past century, modifying specific genomic sequences of the fruit fly has been a difficult, if not impossible, task for Drosophila geneticists. CRISPR/Cas9 truly redefined molecular genetics and provided new tools to model human diseases in Drosophila melanogaster. This is particularly true for genes whose protein sequences are highly conserved. Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme in nucleotide metabolism whose missense mutations are found in a number of neurological disorders. In addition, PRPS is deregulated in cancer, particularly those that become resistant to cancer therapy. Notably, Drosophila PRPS share about 90% protein sequence identity with its human orthologs, making it an ideal gene to study via CRISPR/Cas9. In this review, we will discuss potential applications of Drosophila CRISPR/Cas9 to model PRPS-dependent disorders and other metabolic diseases that are associated with nucleotide metabolism.

 

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