Alfa RW, Kim SK. Using Drosophila to discover mechanisms underlying type 2 diabetes. Dis Model Mech. 2016 Apr 1;9(4):365-76. PMID: 27053133.
From the abstract: "Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. ... Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis."
Friday, April 8, 2016
Monday, March 28, 2016
Fly models used to validate association of proteins with Alzheimers disease
Minjarez B, Calderón-González KG, Rustarazo ML, Herrera-Aguirre ME, Labra-Barrios ML, Rincon-Limas DE, Del Pino MM, Mena R, Luna-Arias JP. Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry. J Proteomics. 2016 Mar 21. PMID: 27012543.
From the abstract: "Alzheimer's disease is one of the leading causes of dementia in the elderly. It is considered the result of complex events involving both genetic and environmental factors. To gain further insights into this complexity, we quantitatively analyzed the proteome of cortex region of brains from patients diagnosed with Alzheimer's disease, using a bottom-up proteomics approach. ... We used Drosophila to validate some of the hits ... We manipulated their homolog genes in Drosophila models of Aβ- and Tau-induced pathology. We found proteins that can either modify Aβ toxicity, Tau toxicity or both, suggesting specific interactions with different pathways. This approach illustrates the potential of Drosophila to validate hits after MS studies and suggest that model organisms should be included in the pipeline to identify relevant targets for Alzheimer's disease. ... With this approach, Sideroflexin and Phosphoglucomutase-1 were identified as novel proteins connected with Alzheimer's disease."
From the abstract: "Alzheimer's disease is one of the leading causes of dementia in the elderly. It is considered the result of complex events involving both genetic and environmental factors. To gain further insights into this complexity, we quantitatively analyzed the proteome of cortex region of brains from patients diagnosed with Alzheimer's disease, using a bottom-up proteomics approach. ... We used Drosophila to validate some of the hits ... We manipulated their homolog genes in Drosophila models of Aβ- and Tau-induced pathology. We found proteins that can either modify Aβ toxicity, Tau toxicity or both, suggesting specific interactions with different pathways. This approach illustrates the potential of Drosophila to validate hits after MS studies and suggest that model organisms should be included in the pipeline to identify relevant targets for Alzheimer's disease. ... With this approach, Sideroflexin and Phosphoglucomutase-1 were identified as novel proteins connected with Alzheimer's disease."
Thursday, March 24, 2016
Drosophila studies help implicate ALFY gene in human primary microcephaly
Kadir R, Harel T, Markus B, Perez Y, Bakhrat A, Cohen I, Volodarsky M, Feintsein-Linial M, Chervinski E, Zlotogora J, Sivan S, Birnbaum RY, Abdu U, Shalev S, Birk OS. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size. PLoS Genet. 2016 Mar 23;12(3):e1005919. PMID: 27008544.
From the abstract: "Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume ... We now show ... that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype ..."
From the abstract: "Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume ... We now show ... that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype ..."
Wednesday, March 9, 2016
Saturday, February 27, 2016
Drosophila model of Alexander disease used to identify cholinergic signaling as potential therapeutic target
Wang L, Hagemann TL, Messing A, Feany MB. An In Vivo Pharmacological Screen Identifies Cholinergic Signaling as a Therapeutic Target in Glial-Based Nervous System Disease. J Neurosci. 2016 Feb 3;36(5):1445-55. PMID: 26843629; PMCID: PMC4737762.
From the abstract: "... Using a simple Drosophila model of Alexander disease, we performed a moderate throughput chemical screen of FDA-approved drugs and natural compounds, and found that reducing muscarinic cholinergic signaling ameliorated clinical symptoms and oxidative stress in Alexander disease model flies and mice. Our work demonstrates that small animal models are valuable screening tools for therapeutic compound identification in complex human diseases and that existing drugs can be a valuable resource for drug discovery given their known pharmacological and safety profiles."
Wondering what is Alexander disease? Read about this rare nervous system disease at NIH Genetics Home Reference.
From the abstract: "... Using a simple Drosophila model of Alexander disease, we performed a moderate throughput chemical screen of FDA-approved drugs and natural compounds, and found that reducing muscarinic cholinergic signaling ameliorated clinical symptoms and oxidative stress in Alexander disease model flies and mice. Our work demonstrates that small animal models are valuable screening tools for therapeutic compound identification in complex human diseases and that existing drugs can be a valuable resource for drug discovery given their known pharmacological and safety profiles."
Wondering what is Alexander disease? Read about this rare nervous system disease at NIH Genetics Home Reference.
Tuesday, February 23, 2016
Detailed phenotypic analysis of flies lacking activity of Nf1, which is associated with neurofibromatosis
King LB, Koch M, Murphy K, Velazquez Y, Ja WW, Tomchik SM. Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila. G3 (Bethesda). 2016 Feb 19. PMID: 26896440.
From the abstract: "Neurofibromatosis I is a common genetic disorder that results in tumor formation and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, sleep, and autism spectrum disorder-like traits. ... Drosophila provide a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. ... Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits."
From the abstract: "Neurofibromatosis I is a common genetic disorder that results in tumor formation and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, sleep, and autism spectrum disorder-like traits. ... Drosophila provide a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. ... Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits."
Saturday, February 20, 2016
Cutting-edge techniques used in Drosophila help elucidate mechanisms of amphetamine transport in cells
Freyberg Z, Sonders MS, Aguilar JI, Hiranita T, Karam CS, Flores J, Pizzo AB, Zhang Y, Farino ZJ, Chen A, Martin CA, Kopajtic TA, Fei H, Hu G, Lin YY, Mosharov EV, McCabe BD, Freyberg R, Wimalasena K, Hsin LW, Sames D, Krantz DE, Katz JL, Sulzer D, Javitch JA. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. Nat Commun. 2016 Feb 16;7:10652. PMID: 26879809.
From the abstract: "Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration ... To study VMAT's role .. we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. ... we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects."
From the abstract: "Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration ... To study VMAT's role .. we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. ... we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects."
Subscribe to:
Posts (Atom)