The interesting argument regarding p53, transposons, and cancer that is presented in this review draws in part from studies done in flies.
Wylie A, Jones AE, Abrams JM. p53 in the game of transposons. Bioessays. 2016 Nov;38(11):1111-1116. PMID: 27644006.
From the abstract: "Throughout the animal kingdom, p53 genes function to restrain mobile elements and recent observations indicate that transposons become derepressed in human cancers. ..."
Thursday, October 27, 2016
Wednesday, October 26, 2016
Review of animal models of SMA
Edens BM, Ajroud-Driss S, Ma L, Ma YC. Molecular mechanisms and animal models of spinal muscular atrophy. Biochim Biophys Acta. 2015 Apr;1852(4):685-92. PMID: 25088406.
Fly, mouse, and human cell models of Duchenne muscular dystrophy used to evaluate exon skipping as a potential therapeutic strategy
Gao QQ, Wyatt E, Goldstein JA, LoPresti P, Castillo LM, Gazda A, Petrossian N, Earley JU, Hadhazy M, Barefield DY, Demonbreun AR, Bönnemann C, Wolf M, McNally EM. Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping. J Clin Invest. 2015 Nov 2;125(11):4186-95. PMID: 26457733; PMCID: PMC4639981.
From the abstract: "Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. ... Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. ... We generated an internally truncated γ-sarcoglycan protein that we have termed Mini-Gamma by deleting a large portion of the extracellular domain. Mini-Gamma provided functional and pathological benefits to correct the loss of γ-sarcoglycan in a Drosophila model, in heterologous cell expression studies, and in transgenic mice lacking γ-sarcoglycan. We generated a cellular model of human muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mutant human γ-sarcoglycan. Since Mini-Gamma represents removal of 4 of the 7 coding exons in γ-sarcoglycan, this approach provides a viable strategy to treat the majority of patients with γ-sarcoglycan gene mutations."
From the abstract: "Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. ... Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. ... We generated an internally truncated γ-sarcoglycan protein that we have termed Mini-Gamma by deleting a large portion of the extracellular domain. Mini-Gamma provided functional and pathological benefits to correct the loss of γ-sarcoglycan in a Drosophila model, in heterologous cell expression studies, and in transgenic mice lacking γ-sarcoglycan. We generated a cellular model of human muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mutant human γ-sarcoglycan. Since Mini-Gamma represents removal of 4 of the 7 coding exons in γ-sarcoglycan, this approach provides a viable strategy to treat the majority of patients with γ-sarcoglycan gene mutations."
Fly model of Alzheimer's disease tested with potentially bioactive viridins extracted from endolichenic fungi
Zhao Q, Chen GD, Feng XL, Yu Y, He RR, Li XX, Huang Y, Zhou WX, Guo LD, Zheng YZ, Yao XS, Gao H. Nodulisporiviridins A-H, Bioactive Viridins from Nodulisporium sp. J Nat Prod. 2015 Jun 26;78(6):1221-30. PMID: 25978520.
From the abstract: "Eight new viridins, nodulisporiviridins A-H (1-8), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was fermented with potato-dextrose broth. ... The short-term memory assay on an Aβ transgenic drosophila model of Alzheimer's disease showed that all eight compounds improved the short-term memory capacity, with potencies close to that of the positive control (memantine)."
From the abstract: "Eight new viridins, nodulisporiviridins A-H (1-8), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was fermented with potato-dextrose broth. ... The short-term memory assay on an Aβ transgenic drosophila model of Alzheimer's disease showed that all eight compounds improved the short-term memory capacity, with potencies close to that of the positive control (memantine)."
Fly eye study related to Alzheimer's disease
Cutler T, Sarkar A, Moran M, Steffensmeier A, Puli OR, Mancini G, Tare M, Gogia N, Singh A. Drosophila Eye Model to Study Neuroprotective Role of CREB Binding Protein (CBP) in Alzheimer's Disease. PLoS One. 2015 Sep 14;10(9):e0137691. PMID: 26367392; PMCID: PMC4569556.
Characterization of sleep in a fly model of epilepsy
Petruccelli E, Lansdon P, Kitamoto T. Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock-In Model of Human Epilepsy. PLoS One. 2015 Sep 11;10(9):e0137758. PMID: 26361221; PMCID: PMC4567262.
From the abstract: "Despite an established link between epilepsy and sleep behavior, it remains unclear how specific epileptogenic mutations affect sleep and subsequently influence seizure susceptibility. ... Here, we show that at room temperature the GEFS+ mutation dominantly modifies sleep, with mutants exhibiting rapid sleep onset at dusk and increased nighttime sleep as compared to controls. ... Additionally, analyses under other light conditions suggested that the GEFS+ mutation led to reduced buffering of behavioral responses to light on and off stimuli, which contributed to characteristic GEFS+ sleep phenotypes. ... Our study has revealed the sleep architecture of a Drosophila VGSC mutant that harbors a human GEFS+ mutation, and provided unique insight into the relationship between sleep and epilepsy."
From the abstract: "Despite an established link between epilepsy and sleep behavior, it remains unclear how specific epileptogenic mutations affect sleep and subsequently influence seizure susceptibility. ... Here, we show that at room temperature the GEFS+ mutation dominantly modifies sleep, with mutants exhibiting rapid sleep onset at dusk and increased nighttime sleep as compared to controls. ... Additionally, analyses under other light conditions suggested that the GEFS+ mutation led to reduced buffering of behavioral responses to light on and off stimuli, which contributed to characteristic GEFS+ sleep phenotypes. ... Our study has revealed the sleep architecture of a Drosophila VGSC mutant that harbors a human GEFS+ mutation, and provided unique insight into the relationship between sleep and epilepsy."
Green-glowing flies used in study relevant to Huntington's disease
Babcock DT, Ganetzky B. Transcellular spreading of huntingtin aggregates in the Drosophila brain. Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):E5427-33. PMID: 26351672; PMCID: PMC4593132.
From the abstract: "A key feature of many neurodegenerative diseases is the accumulation and subsequent aggregation of misfolded proteins. Recent studies have highlighted the transcellular propagation of protein aggregates in several major neurodegenerative diseases, although the precise mechanisms underlying this spreading and how it relates to disease pathology remain unclear. Here we use a polyglutamine-expanded form of human huntingtin (Htt) with a fluorescent tag to monitor the spreading of aggregates in the Drosophila brain in a model of Huntington's disease. ... We show that Htt aggregates cause non-cell-autonomous pathology ..."
From the abstract: "A key feature of many neurodegenerative diseases is the accumulation and subsequent aggregation of misfolded proteins. Recent studies have highlighted the transcellular propagation of protein aggregates in several major neurodegenerative diseases, although the precise mechanisms underlying this spreading and how it relates to disease pathology remain unclear. Here we use a polyglutamine-expanded form of human huntingtin (Htt) with a fluorescent tag to monitor the spreading of aggregates in the Drosophila brain in a model of Huntington's disease. ... We show that Htt aggregates cause non-cell-autonomous pathology ..."
Uncovering cellular mechanisms relevant to Parkinson's Disease
Dodson MW, Leung LK, Lone M, Lizzio MA, Guo M. Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo. Dis Model Mech. 2014 Dec;7(12):1351-63. PMID: 25288684; PMCID: PMC4257004.
Zhou ZD, Xie SP, Sathiyamoorthy S, Saw WT, Sing TY, Ng SH, Chua HP, Tang AM, Shaffra F, Li Z, Wang H, Ho PG, Lai MK, Angeles DC, Lim TM, Tan EK. F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy. Hum Mol Genet. 2015 Nov 15;24(22):6314-30. PMID: 26310625.
Kong Y, Liang X, Liu L, Zhang D, Wan C, Gan Z, Yuan L. High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model. PLoS One. 2015 Sep 11;10(9):e0137432. PMID: 26361355; PMCID: PMC4567341.
Gehrke S, Wu Z, Klinkenberg M, Sun Y, Auburger G, Guo S, Lu B. PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane. Cell Metab. 2015 Jan 6;21(1):95-108. PMID: 25565208; PMCID: PMC4455944.
Shmueli MD, Schnaider L, Herzog G, Gazit E, Segal D. Computational and experimental characterization of dVHL establish a Drosophila model of VHL syndrome. PLoS One. 2014 Oct 13;9(10):e109864. PMID: 25310726; PMCID: PMC4195687.
Dubos A, Castells-Nobau A, Meziane H, Oortveld MA, Houbaert X, Iacono G, Martin C, Mittelhaeuser C, Lalanne V, Kramer JM, Bhukel A, Quentin C, Slabbert J, Verstreken P, Sigrist SJ, Messaddeq N, Birling MC, Selloum M, Stunnenberg HG, Humeau Y, Schenck A, Herault Y. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration. Hum Mol Genet. 2015 Dec 1;24(23):6736-55. PMID: 26376863; PMCID: PMC4634377.
Arsenijevic Y. Cell Cycle Proteins and Retinal Degeneration: Evidences of New Potential Therapeutic Targets. Adv Exp Med Biol. 2016;854:371-7. PMID: 26427434.
Angelova PR, Agrawalla BK, Elustondo PA, Gordon J, Shiba T, Abramov AY, Chang YT, Pavlov EV. In situ investigation of mammalian inorganic polyphosphate localization using novel selective fluorescent probes JC-D7 and JC-D8. ACS Chem Biol. 2014 Sep 19;9(9):2101-10. PMID: 25007079.
van der Merwe C, Jalali Sefid Dashti Z, Christoffels A, Loos B, Bardien S. Evidence for a common biological pathway linking three Parkinson's disease-causing genes: parkin, PINK1 and DJ-1. Eur J Neurosci. 2015 May;41(9):1113-25. PMID: 25761903.
Zhou ZD, Xie SP, Sathiyamoorthy S, Saw WT, Sing TY, Ng SH, Chua HP, Tang AM, Shaffra F, Li Z, Wang H, Ho PG, Lai MK, Angeles DC, Lim TM, Tan EK. F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy. Hum Mol Genet. 2015 Nov 15;24(22):6314-30. PMID: 26310625.
Kong Y, Liang X, Liu L, Zhang D, Wan C, Gan Z, Yuan L. High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model. PLoS One. 2015 Sep 11;10(9):e0137432. PMID: 26361355; PMCID: PMC4567341.
Gehrke S, Wu Z, Klinkenberg M, Sun Y, Auburger G, Guo S, Lu B. PINK1 and Parkin control localized translation of respiratory chain component mRNAs on mitochondria outer membrane. Cell Metab. 2015 Jan 6;21(1):95-108. PMID: 25565208; PMCID: PMC4455944.
Shmueli MD, Schnaider L, Herzog G, Gazit E, Segal D. Computational and experimental characterization of dVHL establish a Drosophila model of VHL syndrome. PLoS One. 2014 Oct 13;9(10):e109864. PMID: 25310726; PMCID: PMC4195687.
Dubos A, Castells-Nobau A, Meziane H, Oortveld MA, Houbaert X, Iacono G, Martin C, Mittelhaeuser C, Lalanne V, Kramer JM, Bhukel A, Quentin C, Slabbert J, Verstreken P, Sigrist SJ, Messaddeq N, Birling MC, Selloum M, Stunnenberg HG, Humeau Y, Schenck A, Herault Y. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration. Hum Mol Genet. 2015 Dec 1;24(23):6736-55. PMID: 26376863; PMCID: PMC4634377.
Arsenijevic Y. Cell Cycle Proteins and Retinal Degeneration: Evidences of New Potential Therapeutic Targets. Adv Exp Med Biol. 2016;854:371-7. PMID: 26427434.
Angelova PR, Agrawalla BK, Elustondo PA, Gordon J, Shiba T, Abramov AY, Chang YT, Pavlov EV. In situ investigation of mammalian inorganic polyphosphate localization using novel selective fluorescent probes JC-D7 and JC-D8. ACS Chem Biol. 2014 Sep 19;9(9):2101-10. PMID: 25007079.
van der Merwe C, Jalali Sefid Dashti Z, Christoffels A, Loos B, Bardien S. Evidence for a common biological pathway linking three Parkinson's disease-causing genes: parkin, PINK1 and DJ-1. Eur J Neurosci. 2015 May;41(9):1113-25. PMID: 25761903.
Characterization of a fly model of glassic galactosemia
Jumbo-Lucioni P, Parkinson W, Broadie K. Overelaborated synaptic architecture and reduced synaptomatrix glycosylation in a Drosophila classic galactosemia disease model. Dis Model Mech. 2014 Dec;7(12):1365-78. PMID: 25326312; PMCID: PMC4257005.
From the abstract: "Classic galactosemia (CG) is an autosomal recessive disorder resulting from loss of galactose-1-phosphate uridyltransferase (GALT), which catalyzes conversion of galactose-1-phosphate and uridine diphosphate (UDP)-glucose to glucose-1-phosphate and UDP-galactose, immediately upstream of UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine synthesis. These four UDP-sugars are essential donors for driving the synthesis of glycoproteins and glycolipids, which heavily decorate cell surfaces and extracellular spaces. In addition to acute, potentially lethal neonatal symptoms, maturing individuals with CG develop striking neurodevelopmental, motor and cognitive impairments. Previous studies suggest that neurological symptoms are associated with glycosylation defects, with CG recently being described as a congenital disorder of glycosylation (CDG), showing defects in both N- and O-linked glycans. Here, we characterize behavioral traits, synaptic development and glycosylated synaptomatrix formation in a GALT-deficient Drosophila disease model. ... These results reveal synaptomatrix glycosylation losses, altered trans-synaptic signaling pathway components, defective synaptogenesis and impaired coordinated movement in a CG neurological disease model."
From the abstract: "Classic galactosemia (CG) is an autosomal recessive disorder resulting from loss of galactose-1-phosphate uridyltransferase (GALT), which catalyzes conversion of galactose-1-phosphate and uridine diphosphate (UDP)-glucose to glucose-1-phosphate and UDP-galactose, immediately upstream of UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine synthesis. These four UDP-sugars are essential donors for driving the synthesis of glycoproteins and glycolipids, which heavily decorate cell surfaces and extracellular spaces. In addition to acute, potentially lethal neonatal symptoms, maturing individuals with CG develop striking neurodevelopmental, motor and cognitive impairments. Previous studies suggest that neurological symptoms are associated with glycosylation defects, with CG recently being described as a congenital disorder of glycosylation (CDG), showing defects in both N- and O-linked glycans. Here, we characterize behavioral traits, synaptic development and glycosylated synaptomatrix formation in a GALT-deficient Drosophila disease model. ... These results reveal synaptomatrix glycosylation losses, altered trans-synaptic signaling pathway components, defective synaptogenesis and impaired coordinated movement in a CG neurological disease model."
Fly study uncovers new information regarding the cellular role of the ALS related gene TDP-43
Miskiewicz K, Jose LE, Yeshaw WM, Valadas JS, Swerts J, Munck S, Feiguin F, Dermaut B, Verstreken P. HDAC6 is a Bruchpilot deacetylase that facilitates neurotransmitter release. Cell Rep. 2014 Jul 10;8(1):94-102. PMID: 24981865.
From the abstract: "... reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion ..."
From the abstract: "... reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion ..."
Report of a "true ortholog" in flies of the human Charcot-Marie-Tooth disease-related gene GDAP1
López Del Amo V, Seco-Cervera M, García-Giménez JL, Whitworth AJ, Pallardó FV, Galindo MI. Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy. Hum Mol Genet. 2015 Jan 1;24(1):21-36. PMID: 25122658.
From the abstract: "One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. ... Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration."
From the abstract: "One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. ... Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration."
Can we outrun aging? Fly study of impact of fatiguing exercise on aging
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."
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."
Fly studies contribute to study focused on centronuclear myopathy
Chin YH, Lee A, Kan HW, Laiman J, Chuang MC, Hsieh ST, Liu YW. Dynamin-2 mutations associated with centronuclear myopathy are hypermorphic and lead to T-tubule fragmentation. Hum Mol Genet. 2015 Oct 1;24(19):5542-54. PMID: 26199319.
From the abstract: "Skeletal muscle requires adequate membrane trafficking and remodeling to maintain its normal structure and functions. Consequently, many human myopathies are caused by mutations in membrane trafficking machinery. The large GTPase dynamin-2 (Dyn2) is best known for catalyzing membrane fission during clathrin-mediated endocytosis (CME), which is critical for cell signaling and survival. Despite its ubiquitous expression, mutations of Dyn2 are associated with two tissue-specific congenital disorders: centronuclear myopathy (CNM) and Charcot-Marie-Tooth (CMT) neuropathy. Several disease models for CNM-Dyn2 have been established ... . ... we found that the expression of CNM-Dyn2 mutants does not impair CME in myoblast, but leads to T-tubule fragmentation in both C2C12-derived myotubes and Drosophila body wall muscle. Our results demonstrate that CNM-Dyn2 mutants are gain-of-function mutations, and their primary effect in muscle is T-tubule disorganization, which explains the susceptibility of muscle to Dyn2 hyperactivity."
From the abstract: "Skeletal muscle requires adequate membrane trafficking and remodeling to maintain its normal structure and functions. Consequently, many human myopathies are caused by mutations in membrane trafficking machinery. The large GTPase dynamin-2 (Dyn2) is best known for catalyzing membrane fission during clathrin-mediated endocytosis (CME), which is critical for cell signaling and survival. Despite its ubiquitous expression, mutations of Dyn2 are associated with two tissue-specific congenital disorders: centronuclear myopathy (CNM) and Charcot-Marie-Tooth (CMT) neuropathy. Several disease models for CNM-Dyn2 have been established ... . ... we found that the expression of CNM-Dyn2 mutants does not impair CME in myoblast, but leads to T-tubule fragmentation in both C2C12-derived myotubes and Drosophila body wall muscle. Our results demonstrate that CNM-Dyn2 mutants are gain-of-function mutations, and their primary effect in muscle is T-tubule disorganization, which explains the susceptibility of muscle to Dyn2 hyperactivity."
Drosophila studies contribute to research on possible links between the metal copper and schizophrenia
Gokhale A, Vrailas-Mortimer A, Larimore J, Comstra HS, Zlatic SA, Werner E, Manvich DF, Iuvone PM, Weinshenker D, Faundez V. Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a schizophrenia susceptibility factor. Hum Mol Genet. 2015 Oct 1;24(19):5512-23. PMID: 26199316; PMCID: PMC4572075.
From the abstract: "Environmental factors and susceptible genomes interact to determine the risk of neurodevelopmental disorders. ... Here we focus on the schizophrenia susceptibility gene DTNBP1 and its product dysbindin, a subunit of the BLOC-1 complex, and describe a neuronal pathway modulating copper metabolism via ATP7A. ... Dysbindin/BLOC-1 loss-of-function alleles do not affect cell and tissue copper content, yet they alter the susceptibility to toxic copper challenges in both mammalian cells and Drosophila. Our results demonstrate that perturbations downstream of the schizophrenia susceptibility gene DTNBP1 confer susceptibility to copper, a metal that in excess is a neurotoxin and whose depletion constitutes a micronutrient deficiency."
From the abstract: "Environmental factors and susceptible genomes interact to determine the risk of neurodevelopmental disorders. ... Here we focus on the schizophrenia susceptibility gene DTNBP1 and its product dysbindin, a subunit of the BLOC-1 complex, and describe a neuronal pathway modulating copper metabolism via ATP7A. ... Dysbindin/BLOC-1 loss-of-function alleles do not affect cell and tissue copper content, yet they alter the susceptibility to toxic copper challenges in both mammalian cells and Drosophila. Our results demonstrate that perturbations downstream of the schizophrenia susceptibility gene DTNBP1 confer susceptibility to copper, a metal that in excess is a neurotoxin and whose depletion constitutes a micronutrient deficiency."
Modeling neurodegenerative disease
Lepesant JA. The promises of neurodegenerative disease modeling. C R Biol. 2015 Aug-Sep;338(8-9):584-92. PMID: 26210484.
From the abstract: "The rise in the prevalence of neurodegenerative diseases parallels the rapid increase in human lifespan. Despite intensive research, the molecular and cellular mechanisms underlying the onset and progression of these devastating diseases with age are still poorly understood. ... This review will focus on the advantages offered by the genetic tools available in Drosophila for combining powerful strategies in order to tackle the causative factors of these complex pathologies and help to elaborate efficient drugs to treat them."
From the abstract: "The rise in the prevalence of neurodegenerative diseases parallels the rapid increase in human lifespan. Despite intensive research, the molecular and cellular mechanisms underlying the onset and progression of these devastating diseases with age are still poorly understood. ... This review will focus on the advantages offered by the genetic tools available in Drosophila for combining powerful strategies in order to tackle the causative factors of these complex pathologies and help to elaborate efficient drugs to treat them."
Thursday, October 6, 2016
Preprint describes new fly model of Saposin deficiency
A Saposin deficiency model in Drosophila: lysosomal storage, progressive neurodegeneration, sensory physiological decline and defective calcium homeostasis
J Hindle, Sarita Hebbar, Dominik Schwudke, Christopher J Elliott, Sean T Sweeney
doi: http://dx.doi.org/10.1101/078725
From the abstract: "Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases in the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. ..."
J Hindle, Sarita Hebbar, Dominik Schwudke, Christopher J Elliott, Sean T Sweeney
doi: http://dx.doi.org/10.1101/078725
From the abstract: "Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases in the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. ..."
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