scholarly journals The Fruit Fly Drosophila melanogaster as a Model System to Study Cholesterol Metabolism and Homeostasis

Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ryusuke Niwa ◽  
Yuko S. Niwa
Keyword(s):  
Drosophila Melanogaster ◽  
Steroid Hormones ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Fruit Fly ◽  
Model System ◽  
Biophysical Properties ◽  
Type C ◽  
Niemann Pick

Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently, genetic approaches in the fruit fly, Drosophila melanogaster, have been successfully used for the analysis of molecular mechanisms that regulate cholesterol metabolism and homeostasis. This paper summarizes the recent studies on genes that regulate cholesterol metabolism and homeostasis, including neverland, Niemann Pick type C(NPC) disease genes, and DHR96.

Model construction of Niemann-Pick type C disease in zebrafish

2018 ◽  
Vol 399 (8) ◽  
pp. 903-910 ◽  
Author(s):  
Yusheng Lin ◽  
Xiaolian Cai ◽  
Guiping Wang ◽  
Gang Ouyang ◽  
Hong Cao
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Lipid Profiling ◽  
Zebrafish Model ◽  
Reduced Body ◽  
Significant Difference ◽  
Abnormal Accumulation ◽  
Purkinje Cell Death ◽  
Type C ◽  
Niemann Pick

Abstract Niemann-Pick type C disease (NPC) is a rare human disease, with limited effective treatment options. Most cases of NPC disease are associated with inactivating mutations of the NPC1 gene. However, cellular and molecular mechanisms responsible for the NPC1 pathogenesis remain poorly defined. This is partly due to the lack of a suitable animal model to monitor the disease progression. In this study, we used CRISPR to construct an NPC1−/− zebrafish model, which faithfully reproduced the cardinal pathological features of this disease. In contrast to the wild type (WT), the deletion of NPC1 alone caused significant hepatosplenomegaly, ataxia, Purkinje cell death, increased lipid storage, infertility and reduced body length and life span. Most of the NPC1−/− zebrafish died within the first month post fertilization, while the remaining specimens developed slower than the WT and died before reaching 8 months of age. Filipin-stained hepatocytes of the NPC1−/− zebrafish were clear, indicating abnormal accumulation of unesterified cholesterol. Lipid profiling showed a significant difference between NPC1−/− and WT zebrafish. An obvious accumulation of seven sphingolipids was detected in livers of NPC1−/− zebrafish. In summary, our results provide a valuable model system that could identify promising therapeutic targets and treatments for the NPC disease.

scholarly journals ACAT1-associated Late Endosomes/Lysosomes Significantly Improve Impaired Intracellular Cholesterol Metabolism and the Survival of Niemann-Pick Type C Mice

2014 ◽  
Vol 47 (2) ◽  
pp. 35-43 ◽  
Author(s):  
Masashi Kamikawa ◽  
XiaoFeng Lei ◽  
Yukio Fujiwara ◽  
Kazuchika Nishitsuji ◽  
Hiroshi Mizuta ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Late Endosomes ◽  
Type C ◽  
Intracellular Cholesterol ◽  
Niemann Pick

scholarly journals Embryonic Striatal Neurons from Niemann-Pick Type C Mice Exhibit Defects in Cholesterol Metabolism and Neurotrophin Responsiveness

2000 ◽  
Vol 275 (26) ◽  
pp. 20179-20187 ◽  
Author(s):  
Leslie P. Henderson ◽  
Li Lin ◽  
Anita Prasad ◽  
Colleen A. Paul ◽  
Ta Yuan Chang ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Striatal Neurons ◽  
Type C ◽  
Niemann Pick

scholarly journals First person – Laura Tamberg

2020 ◽  
Vol 13 (7) ◽  
pp. dmm046532
Keyword(s):  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Model System ◽  
Early Career ◽  
Disease Models ◽  
First Person ◽  
Early Career Researchers ◽  
University Of Technology ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Laura Tamberg is first author on ‘Daughterless, the Drosophila orthologue of TCF4, is required for associative learning and maintenance of the synaptic proteome’, published in DMM. Laura is a PhD student in the lab of Tõnis Timmusk at the Tallinn University of Technology, Tallinn, Estonia. Her research involves investigating the use of Drosophila melanogaster as a model system to understand the molecular mechanisms underlying transcription factor TCF4-related neuronal diseases.

scholarly journals Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C

2019 ◽  
Vol 20 (20) ◽  
pp. 5018 ◽  
Author(s):  
Maekawa ◽  
Jinnoh ◽  
Matsumoto ◽  
Narita ◽  
Mashima ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hydrogen Abstraction ◽  
Autosomal Recessive Disorder ◽  
Good Prognosis ◽  
Disease Type ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

: Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation–tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509.

scholarly journals Programmed cell death takes flight: genetic and genomic approaches to gene discovery in Drosophila

2002 ◽  
Vol 9 (2) ◽  
pp. 59-69 ◽  
Author(s):  
S. Gorski ◽  
M. Marra
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Programmed Cell Death ◽  
Gene Discovery ◽  
Fruit Fly ◽  
Model System ◽  
Physiological Process ◽  
Wide Spread ◽  
Cell Death Gene ◽  
Genetics And Genomics

Programmed cell death (PCD) is an essential and wide-spread physiological process that results in the elimination of cells. Genes required to carry out this process have been identified, and many of these remain the subjects of intense investigation. Here, we describe PCD, its functions, and some of the consequences when it goes awry. We review PCD in the model system, the fruit fly, Drosophila melanogaster, with a particular emphasis on cell death gene discovery resulting from both genetics and genomics-based approaches.

scholarly journals Genomic instability and cancer: lessons from Drosophila

Open Biology ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 200060
Author(s):  
Stephan U. Gerlach ◽  
Héctor Herranz
Keyword(s):  
Drosophila Melanogaster ◽  
Animal Models ◽  
Disease Progression ◽  
Genomic Instability ◽  
Genetic Disease ◽  
Current Knowledge ◽  
Fruit Fly ◽  
Model System ◽  
Human Tumours ◽  
Gradual Accumulation

Cancer is a genetic disease that involves the gradual accumulation of mutations. Human tumours are genetically unstable. However, the current knowledge about the origins and implications of genomic instability in this disease is limited. Understanding the biology of cancer requires the use of animal models. Here, we review relevant studies addressing the implications of genomic instability in cancer by using the fruit fly, Drosophila melanogaster , as a model system. We discuss how this invertebrate has helped us to expand the current knowledge about the mechanisms involved in genomic instability and how this hallmark of cancer influences disease progression.

scholarly journals Specification and Patterning of Drosophila Appendages

2018 ◽  
Vol 6 (3) ◽  
pp. 17 ◽  
Author(s):  
Mireya Ruiz-Losada ◽  
David Blom-Dahl ◽  
Sergio Córdoba ◽  
Carlos Estella
Keyword(s):  
Drosophila Melanogaster ◽  
Signaling Pathways ◽  
Imaginal Disc ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
The Body ◽  
Developmental Studies ◽  
Insect Wing ◽  
Environment Exploration ◽  
Larva Development

Appendages are external projections of the body that serve the animal for locomotion, feeding, or environment exploration. The appendages of the fruit fly Drosophila melanogaster are derived from the imaginal discs, epithelial sac-like structures specified in the embryo that grow and pattern during larva development. In the last decades, genetic and developmental studies in the fruit fly have provided extensive knowledge regarding the mechanisms that direct the formation of the appendages. Importantly, many of the signaling pathways and patterning genes identified and characterized in Drosophila have similar functions during vertebrate appendage development. In this review, we will summarize the genetic and molecular mechanisms that lead to the specification of appendage primordia in the embryo and their posterior patterning during imaginal disc development. The identification of the regulatory logic underlying appendage specification in Drosophila suggests that the evolutionary origin of the insect wing is, in part, related to the development of ventral appendages.

scholarly journals Drosophila melanogaster: A Veritable Genetic Tool and in vivo Model for Human Alzheimer’s Disease

2019 ◽  
pp. 1-9
Author(s):  
Oluwatosin Imoleayo, Oyeniran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Human Diseases ◽  
Model Organisms ◽  
In Vivo Model ◽  
Brain Functions ◽  
Drosophila Models

The rise in the cases of neurodegenerative diseases, such as the familial forms of Alzheimer’s disease is worrisome and a burden to many societies in our ever-increasing world. Due to the complexity in the nature of the brain and spinal cord characterized by an extremely organized network of neuronal cells, there is a need to answer scientific inquiries in uncomplicated, though similar, systems. Drosophila melanogaster (fruit-fly) is a well-studied and easily managed genetic model organism used for discerning the molecular mechanisms of many human diseases. There are strong conservations of several basic biological, physiological and neurological features between D. melanogaster and mammals, as about 75% of all human disease-causing genes are considered to possess a functional homolog in the fruit-fly. The development of Drosophila models of several neurodegenerative disorders via developed transgenic technologies has presented spectacular similarities to human diseases. An advantage that the fruit-fly has over other model organisms, such as the mouse, is its comparatively brief lifespan, which allows complex inquiries about brain functions to be addressed more quickly. Furthermore, there have been steady increases in understanding the pathophysiological basis of many neurological disorders via genetic screenings with the aid of Drosophila models. This review presents a widespread summary of the fruit-fly models relevant to Alzheimer’s disease, and highlight important genetic modifiers that have been recognized using this model.

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