Zheng L, Feng Y, Wen DT, Wang H, Wu XS. Fatiguing exercise initiated later in life reduces incidence of fibrillation and improves sleep quality in Drosophila. Age (Dordr). 2015 Aug;37(4):9816. PMID: 26206392; PMCID: PMC4512962.
From the abstract: "As the human body ages, the risk of heart disease and stroke greatly increases. While there is evidence that lifelong exercise is beneficial to the heart's health, the effects of beginning exercise later in life remain unclear. This study aimed to investigate whether exercise training started later in life is beneficial to cardiac aging in Drosophila. ... We found that 2.0 and 2.5 h of exercise caused exercise-induced fatigue, and fatiguing exercise is beneficial for cardiac and healthy aging overall. This study provides a basis for further study in humans on the impact of beginning an exercise regimen later in life on cardiac health. "
Thursday, August 20, 2015
Flies, podocytes and diabetic nephropathy
Na J, Sweetwyne MT, Park AS, Susztak K, Cagan RL. Diet-Induced Podocyte Dysfunction in Drosophila and Mammals. Cell Rep. 2015 Jul 28;12(4):636-47. PMID: 26190114; PMCID: PMC4532696.
From the abstract: "Diabetic nephropathy is a major cause of end-stage kidney disease. Characterized by progressive microvascular disease, most efforts have focused on injury to the glomerular endothelium. Recent work has suggested a role for the podocyte, a highly specialized component of the glomerular filtration barrier. Here, we demonstrate that the Drosophila nephrocyte, a cell analogous to the mammalian podocyte, displays defects that phenocopy aspects of diabetic nephropathy in animals fed chronic high dietary sucrose. Through functional studies, we identify an OGT-Polycomb-Knot-Sns pathway that links dietary sucrose to loss of the Nephrin ortholog Sns ..."
From the abstract: "Diabetic nephropathy is a major cause of end-stage kidney disease. Characterized by progressive microvascular disease, most efforts have focused on injury to the glomerular endothelium. Recent work has suggested a role for the podocyte, a highly specialized component of the glomerular filtration barrier. Here, we demonstrate that the Drosophila nephrocyte, a cell analogous to the mammalian podocyte, displays defects that phenocopy aspects of diabetic nephropathy in animals fed chronic high dietary sucrose. Through functional studies, we identify an OGT-Polycomb-Knot-Sns pathway that links dietary sucrose to loss of the Nephrin ortholog Sns ..."
Wednesday, August 19, 2015
New fly model of ALS -- temporarl and spatial control of TDP-43 expression
Cheng CW, Lin MJ, Shen CJ. Rapamycin Alleviates Pathogenesis of a New Drosophila Model of ALS-TDP. J Neurogenet. 2015 Jul 29:1-47. PMID: 26219309.
From the abstract: "... We describe the generation and characterization of a new fly model of ALS-TDP with transgenic expression of the Drosophila ortholog of TDP-43, dTDP, in adult flies under the control of a temperature sensitive motor neuron-specific GAL4, thus bypassing the deleterious effect of dTDP during development. ... In sum, this Drosophila model of ALS-TDP under temporal and spatial control presents a useful new genetic tool for the screening and validation of therapeutic drugs for ALS. Furthermore, the data support our previous finding that autophagy activators including rapamycin are potential therapeutic drugs for the progression of neurodegenerative diseases with TDP-43 proteinopathies."
From the abstract: "... We describe the generation and characterization of a new fly model of ALS-TDP with transgenic expression of the Drosophila ortholog of TDP-43, dTDP, in adult flies under the control of a temperature sensitive motor neuron-specific GAL4, thus bypassing the deleterious effect of dTDP during development. ... In sum, this Drosophila model of ALS-TDP under temporal and spatial control presents a useful new genetic tool for the screening and validation of therapeutic drugs for ALS. Furthermore, the data support our previous finding that autophagy activators including rapamycin are potential therapeutic drugs for the progression of neurodegenerative diseases with TDP-43 proteinopathies."
Wednesday, August 5, 2015
Review--fly models of Huntington's disease
Using Drosophila models of Huntington's disease as a translatable tool. http://t.co/lXw6IQDTa4
— flypapers (@fly_papers) August 5, 2015
From the abstract: "there has been a significant contribution to our understating of the disease from studies utilizing Drosophila melanogaster. Flies have a Htt protein, so the endogenous pathways with which it interacts are likely conserved. Transgenic flies engineered to overexpress the human mutant HTT gene display protein aggregation, neurodegeneration, behavioural deficits and a reduced lifespan. The short life span of flies, low cost of maintaining stocks and genetic tools available for in vivo manipulation make them ideal for the discovery of new genes that are involved in HD pathology."
Tuesday, August 4, 2015
Adult fly leg as "valuable new tool" for study of TDP-43-mediated degeneration of motor neurons
Sreedharan J, Neukomm LJ, Brown RH Jr, Freeman MR. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Curr Biol. 2015 Jul 28. pii: S0960-9822(15)00739-3. PMID: 26234214.
From the abstract: "The RNA-processing protein TDP-43 is central to the pathogenesis of amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron (MN) disease [1-4]. TDP-43 is conserved in Drosophila ... We used a mosaic approach to study age-dependent MN loss in the adult fly leg where it is possible to resolve single motor axons, NMJs and active zones, and perform rapid forward genetic screens. We show that expression of TDP-43Q331K caused dying-back of NMJs and axons ... We report the identification of three genes that suppress TDP-43 toxicity ... In addition to delineating genetic factors that modify TDP-43 toxicity, these results establish the Drosophila adult leg as a valuable new tool for the in vivo study of adult MN phenotypes."
From the abstract: "The RNA-processing protein TDP-43 is central to the pathogenesis of amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron (MN) disease [1-4]. TDP-43 is conserved in Drosophila ... We used a mosaic approach to study age-dependent MN loss in the adult fly leg where it is possible to resolve single motor axons, NMJs and active zones, and perform rapid forward genetic screens. We show that expression of TDP-43Q331K caused dying-back of NMJs and axons ... We report the identification of three genes that suppress TDP-43 toxicity ... In addition to delineating genetic factors that modify TDP-43 toxicity, these results establish the Drosophila adult leg as a valuable new tool for the in vivo study of adult MN phenotypes."
Methods review -- use of fly to model early stages of Alzheimer's disease
Lim JY, Ott S, Crowther DC. Drosophila melanogaster as a Model for Studies on the Early Stages of Alzheimer's Disease. Methods Mol Biol. 2016;1303:227-39. PMID: 26235070.
Review highlights usefulness of Drosophila as a model for study of congenital heart disease
Vogler G, Bodmer R. Cellular Mechanisms of Drosophila Heart Morphogenesis. J Cardiovasc Dev Dis. 2015 Mar 1;2(1):2-16. PMID: 26236710
From the abstract: "Many of the major discoveries in the fields of genetics and developmental biology have been made using the fruit fly, Drosophila melanogaster. With regard to heart development, the conserved network of core cardiac transcription factors that underlies cardiogenesis has been studied in great detail in the fly, and the importance of several signaling pathways that regulate heart morphogenesis, such as Slit/Robo, was first shown in the fly model. ... The specific limitations of the various cardiac model systems currently employed (mammalian and fish models) provide a niche for the fly model ... Here, we review recent advances made using the Drosophila embryo that identify factors relevant for heart formation. ..."
From the abstract: "Many of the major discoveries in the fields of genetics and developmental biology have been made using the fruit fly, Drosophila melanogaster. With regard to heart development, the conserved network of core cardiac transcription factors that underlies cardiogenesis has been studied in great detail in the fly, and the importance of several signaling pathways that regulate heart morphogenesis, such as Slit/Robo, was first shown in the fly model. ... The specific limitations of the various cardiac model systems currently employed (mammalian and fish models) provide a niche for the fly model ... Here, we review recent advances made using the Drosophila embryo that identify factors relevant for heart formation. ..."
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