Zhu ZJ, Wu KC, Qian ZM, Yung WH, Ke Y. Drosophila models for studying iron-related neurodegenerative diseases. Sheng Li Xue Bao. 2014 Feb 25;66(1):47-54. PMID: 24553869.
From the abstract: "In recent years, iron has been regarded as a common pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Friedreich's ataxia (FRDA). ... characteristics ... turn Drosophila into an excellent in vivo genetic system for screening iron-related modifiers in different neurodegenerative conditions ... "
Thursday, May 28, 2015
Review looks at fly and mouse models of Fragile X syndrome
Santos AR, Kanellopoulos AK, Bagni C. Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us. Learn Mem. 2014 Sep 16;21(10):543-55. PMID: 25227249; PMCID: PMC4175497.
From the abstract: "... Here, we review to which extent these biological models are affected by the absence of FMRP, pointing out the similarities with the observed human dysfunction. Additionally, we discuss several potential treatments under study in animal models that are able to partially revert some of the FXS abnormalities. "
From the abstract: "... Here, we review to which extent these biological models are affected by the absence of FMRP, pointing out the similarities with the observed human dysfunction. Additionally, we discuss several potential treatments under study in animal models that are able to partially revert some of the FXS abnormalities. "
Fly study related to ALS points to possible new direction for therapeutic development
Chang JC, Hazelett DJ, Stewart JA, Morton DB. Motor neuron expression of the voltage-gated calcium channel cacophony restores locomotion defects in a Drosophila, TDP-43 loss of function model of ALS. Brain Res. 2014 Oct 10;1584:39-51. PMID: 24275199; PMCID: PMC4031311.
From the abstract: "Dysfunction of the RNA-binding protein, TDP-43, is strongly implicated as a causative event in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). ... Using Drosophila melanogaster to model TDP-43 loss of function, we show that reduced levels of the voltage-gated calcium channel, cacophony, mediate some of the physiological effects of TDP-43 loss. ... Restoring the levels of cacophony in all neurons or selectively in motor neurons rescued these locomotion defects. ... If similar effects of cacophony or related calcium channels are found in human ALS patients, these could be targets for the development of pharmacological therapies for ALS."
From the abstract: "Dysfunction of the RNA-binding protein, TDP-43, is strongly implicated as a causative event in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). ... Using Drosophila melanogaster to model TDP-43 loss of function, we show that reduced levels of the voltage-gated calcium channel, cacophony, mediate some of the physiological effects of TDP-43 loss. ... Restoring the levels of cacophony in all neurons or selectively in motor neurons rescued these locomotion defects. ... If similar effects of cacophony or related calcium channels are found in human ALS patients, these could be targets for the development of pharmacological therapies for ALS."
Wednesday, May 27, 2015
FlyRNAi: in vivo RNAi screen for "flyabetes" phenotype reve...
FlyRNAi: in vivo RNAi screen for "flyabetes" phenotype reve...: Ugrankar R, Berglund E, Akdemir F, Tran C, Kim MS, Noh J, Schneider R, Ebert B, Graff JM. Drosophila glucome screening identifies Ck1alpha a...
Tuesday, May 26, 2015
FlyRNAi: IMP integrative tool for functional genomics updat...
FlyRNAi: IMP integrative tool for functional genomics updat...: Wong AK, Krishnan A, Yao V, Tadych A, Troyanskaya OG. IMP 2.0: a multi-species functional genomics portal for integration, visualization and...
Fly model links zinc to kidney stones, opening possible new routes to prevention and treatment
Chi T, Kim MS, Lang S, Bose N, Kahn A, Flechner L, Blaschko SD, Zee T, Muteliefu G, Bond N, Kolipinski M, Fakra SC, Mandel N, Miller J, Ramanathan A, Killilea DW, Brückner K, Kapahi P, Stoller ML. A Drosophila model identifies a critical role for zinc in mineralization for kidney stone disease. PLoS One. 2015 May 13;10(5):e0124150. PMID: 25970330; PMCID: PMC4430225.
From the abstract: "... Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches."
From the abstract: "... Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches."
Review includes contribution of model systems to understanding lipodystrophies and dyslipidemias
Prieur X, Le May C, Magré J, Cariou B. Congenital lipodystrophies and dyslipidemias. Curr Atheroscler Rep. 2014 Sep;16(9):437. PMID: 25047893.
From the abstract: "... The precise mechanisms by which the lack of adipose tissue causes dyslipidemia remain largely unknown. In recent years, new insights have arisen from data obtained in vitro in adipocytes, yeast, drosophila, and very recently in several genetically modified mouse models of generalized lipodystrophy. ..."
From the abstract: "... The precise mechanisms by which the lack of adipose tissue causes dyslipidemia remain largely unknown. In recent years, new insights have arisen from data obtained in vitro in adipocytes, yeast, drosophila, and very recently in several genetically modified mouse models of generalized lipodystrophy. ..."
Drosophila study related to Renpenning syndrome
Wan D, Zhang ZC, Zhang X, Li Q, Han J. X-chromosome-linked intellectual disability protein PQBP1 associates with and regulates the translation of specific mRNAs. Hum Mol Genet. 2015 May 22. pii: ddv191. PMID: 26002102.
From the abstract: "X-chromosome-linked intellectual disability (XLID) is a common developmental disorder, and mutations of the polyglutamine-binding protein 1 (PQBP1) gene have been linked to this disease. ... Here, we show that the Drosophila homolog of PQBP1 (dPQBP1) is present in the cytoplasm of photoreceptor cells, and its loss results in defective rhabdomere morphogenesis ... also show that dPQBP1 regulates mRNA translation by interacting with dFMR1 ... Our findings reveal the conserved function of PQBP1 in mRNA translation and provide molecular insights into the pathogenic mechanisms underlying Renpenning syndrome."
From the abstract: "X-chromosome-linked intellectual disability (XLID) is a common developmental disorder, and mutations of the polyglutamine-binding protein 1 (PQBP1) gene have been linked to this disease. ... Here, we show that the Drosophila homolog of PQBP1 (dPQBP1) is present in the cytoplasm of photoreceptor cells, and its loss results in defective rhabdomere morphogenesis ... also show that dPQBP1 regulates mRNA translation by interacting with dFMR1 ... Our findings reveal the conserved function of PQBP1 in mRNA translation and provide molecular insights into the pathogenic mechanisms underlying Renpenning syndrome."
Wednesday, May 13, 2015
Experiments in Drosophila, rats and fish contribute to study related to steroid-resistant nephrotic syndrome (SRNS)
Gee HY, Zhang F, Ashraf S, Kohl S, Sadowski CE, Vega-Warner V, Zhou W, Lovric S, Fang H, Nettleton M, Zhu JY, Hoefele J, Weber LT, Podracka L, Boor A, Fehrenbach H, Innis JW, Washburn J, Levy S, Lifton RP, Otto EA, Han Z, Hildebrandt F. KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. J Clin Invest. 2015 May 11. pii: 79504. PMID: 25961457.
From the abstract: "Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of progressive renal function decline and affects millions of people. In a recent study, 30% of SRNS cases evaluated were the result of monogenic mutations in 1 of 27 different genes. Here, ... we identified recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2, and KANK4 in individuals with nephrotic syndrome. In an independent functional genetic screen of Drosophila cardiac nephrocytes, which are equivalents of mammalian podocytes, we determined that the Drosophila KANK homolog (dKank) is essential for nephrocyte function. ..."
From the abstract: "Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of progressive renal function decline and affects millions of people. In a recent study, 30% of SRNS cases evaluated were the result of monogenic mutations in 1 of 27 different genes. Here, ... we identified recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2, and KANK4 in individuals with nephrotic syndrome. In an independent functional genetic screen of Drosophila cardiac nephrocytes, which are equivalents of mammalian podocytes, we determined that the Drosophila KANK homolog (dKank) is essential for nephrocyte function. ..."
'Locomotor signature' suggests fly model can be useful for ADHD-related studies
van der Voet M, Harich B, Franke B, Schenck A. ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila. Mol Psychiatry. 2015 May 12. doi: 10.1038/mp.2015.55. PMID: 25962619.
From the abstract: "Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. ... Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. ..."
From the abstract: "Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. ... Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. ..."
Tuesday, May 12, 2015
Fly cancer model study--linking cell polarity, JNK signaling and the GTPase Rho1
Ma X, Chen Y, Zhang S, Xu W, Shao Y, Yang Y, Li W, Li M, Xue L. Rho1-Wnd signaling regulates loss-of-cell polarity-induced cell invasion in Drosophila. Oncogene. 2015 May 11. PMID: 25961917.
From the abstract: "Both cell polarity and c-Jun N-terminal kinase (JNK) activity are essential to the maintenance of tissue homeostasis, and disruption of either is commonly seen in cancer progression. ... We show that Wallenda (Wnd), a protein kinase of the mitogen-activated protein kinase kinase kinase family, by forming a complex with the GTPase Rho1, is both necessary and sufficient for Rho1-induced JNK-dependent cell invasion, MMP1 activation and epithelial-mesenchymal transition. ... our data not only provides a novel mechanistic insight on how cell polarity loss contributes to cell invasion, but also highlights the value of the Drosophila model system to explore human cancer biology."
From the abstract: "Both cell polarity and c-Jun N-terminal kinase (JNK) activity are essential to the maintenance of tissue homeostasis, and disruption of either is commonly seen in cancer progression. ... We show that Wallenda (Wnd), a protein kinase of the mitogen-activated protein kinase kinase kinase family, by forming a complex with the GTPase Rho1, is both necessary and sufficient for Rho1-induced JNK-dependent cell invasion, MMP1 activation and epithelial-mesenchymal transition. ... our data not only provides a novel mechanistic insight on how cell polarity loss contributes to cell invasion, but also highlights the value of the Drosophila model system to explore human cancer biology."
Genetic modifiers of mutant tRNA synthetases--fly research relevant to Charcot-Marie-Tooth disease
Ermanoska B, Motley WW, Leitão-Gonçalves R, Asselbergh B, Lee LH, De Rijk P, Sleegers K, Ooms T, Godenschwege TA, Timmerman V, Fischbeck KH, Jordanova A. CMT-associated mutations in glycyl- and tyrosyl-tRNA synthetases exhibit similar pattern of toxicity and share common genetic modifiers in Drosophila. Neurobiol Dis. 2014 Aug;68:180-9. PMID: 24807208; PMCID: PMC4086162.
From the abstract: "Aminoacyl-tRNA synthetases are ubiquitously expressed proteins that charge tRNAs with their cognate amino acids. By ensuring the fidelity of protein synthesis, these enzymes are essential for the viability of every cell. Yet, mutations in six tRNA synthetases specifically affect the peripheral nerves and cause Charcot-Marie-Tooth (CMT) disease. ... Our study presents genetic evidence for common mutant-specific interactions between two CMT-associated aminoacyl-tRNA synthetases, lending support for a shared mechanism responsible for the synthetase-induced peripheral neuropathies. "
From the abstract: "Aminoacyl-tRNA synthetases are ubiquitously expressed proteins that charge tRNAs with their cognate amino acids. By ensuring the fidelity of protein synthesis, these enzymes are essential for the viability of every cell. Yet, mutations in six tRNA synthetases specifically affect the peripheral nerves and cause Charcot-Marie-Tooth (CMT) disease. ... Our study presents genetic evidence for common mutant-specific interactions between two CMT-associated aminoacyl-tRNA synthetases, lending support for a shared mechanism responsible for the synthetase-induced peripheral neuropathies. "
Review -- fly models and Parkinson's disease
West RJ, Furmston R, Williams CA, Elliott CJ. Neurophysiology of Drosophila models of Parkinson's disease. Parkinsons Dis. 2015;2015:381281. PMID: 25960916.
The authors outline several pluses of the fly system, including stating that "... Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. ..."
The authors outline several pluses of the fly system, including stating that "... Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. ..."
Wednesday, May 6, 2015
Review discusses possibility of fly as a model for study of relationships between sleep and psychiatric disease
Zordan MA, Sandrelli F. Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say? Front Neurol. 2015 Apr 20;6:80. PMID: 25941512.
From the abstract: "… We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease."
From the abstract: "… We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease."
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