Wednesday, November 19, 2014

Nedd4 in fly and rodent models of Parkinson's disease

Davies SE, Hallett PJ, Moens T, Smith G, Mangano E, Kim HT, Goldberg AL, Liu JL, Isacson O, Tofaris GK. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiol Dis. 2014 Apr;64:79-87. PMID: 24388974; PMCID: PMC3988924.

From the abstract: "... Here we asked whether Nedd4-mediated degradation protects against α-synuclein-induced toxicity in the Drosophila and rodent models of Parkinson's disease. We show that overexpression of Nedd4 can rescue the degenerative phenotype from ectopic expression of α-synuclein in the Drosophila eye. ..."

Several recent reports--fly models of neurodegenerative diseases

Phom L, Achumi B, Alone DP, Muralidhara M, Yenisetti SC. Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease is Phase Specific: Implication of its Therapeutic Effectiveness. Rejuvenation Res. 2014 Sep 19. PMID: 25238331.

Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IO, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EM, Partridge L, Isaacs AM. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science. 2014 Sep 5;345(6201):1192-4. PMID: 25103406.

Latypova EM, Timoshenko SI, Kislik GA, Vitek MP, Schwarzman AL, Sarantseva SV. [Investigation of neuroprotective activity of apolipoprotein E peptide mimetic Cog1410 in transgenic lines of drosophila melanogaster.]. Biomed Khim. 2014 Jul;60(4):515-521. [article in Russian.] PMID: 25249536.

Liao J, Morin LW, Ahmad ST. Methods to Characterize Spontaneous and Startle-induced Locomotion in a Rotenone-induced Parkinson's Disease Model of Drosophila. J Vis Exp. 2014 Aug 17;(90). PMID: 25178101.

Buhlman L, Damiano M, Bertolin G, Ferrando-Miguel R, Lombès A, Brice A, Corti O. Functional interplay between Parkin and Drp1 in mitochondrial fission and clearance. Biochim Biophys Acta. 2014 Sep;1843(9):2012-26. PMID: 24878071.

Marcora MS, Fernández-Gamba AC, Avendaño LA, Rotondaro C, Podhajcer OL, Vidal R, Morelli L, Ceriani MF, Castaño EM. Amyloid peptides ABri and ADan show differential neurotoxicity in transgenic Drosophila models of familial British and Danish dementia. Mol Neurodegener. 2014 Jan 9;9:5. PMID: 24405716; PMCID: PMC3898387.  From the abstract: "Familial British and Familial Danish dementias (FBD and FDD, respectively) are associated with mutations in the BRI2 gene. ... In this work we have modeled FBD and FDD in Drosophila and tested the hypothesis that ABri and ADan are differentially neurotoxic."

Monday, November 17, 2014

Flies used in a study related to Lambert-Eaton Myasthenic Syndrome and Nonprogressive Motor Neuropathy

Herrmann DN, Horvath R, Sowden JE, Gonzales M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014 Sep 4;95(3):332-9. PMID: 25192047; PMCID: PMC4157148.

From the abstract: "... Characterization of the mutation homologous to the human c.920A>C variant in Drosophila Synaptotagmin revealed a dominant disruption of synaptic vesicle exocytosis using this transgenic model. ..."

'Spliceosensor' in flies for high-throughput screening related to myotonic dystrophy

García-Alcover I, Colonques-Bellmunt J, Garijo R, Tormo JR, Artero R, Alvarez-Abril MC, López Castel A, Pérez Alonso M. Development of a Drosophila melanogaster spliceosensor system for in vivo high-throughput screening in myotonic dystrophy type 1. Dis Model Mech. 2014 Sep 19. pii: dmm.016592. PMID: 25239918.

From the abstract: "... This powerful Drosophila-based screening tool might also be applied in other  disease models displaying abnormal alternative splicing, thus offering myriad uses in drug discovery."

Friday, November 14, 2014

Review--insights from fly and mouse models of Fragile X

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):543-555. PMID: 25227249.

Impaired GABAergic circuit structure and function reported for fly model of Fragile-X syndrome

Gatto CL, Pereira D, Broadie K. GABAergic circuit dysfunction in the Drosophila Fragile X syndrome model. Neurobiol Dis. 2014 May;65:142-59. PMID: 24423648; PMCID: PMC3988906.

Fly model of Alzheimer's disease--Finding what's not?

Lüchtenborg AM, Katanaev VL. Lack of evidence of the interaction of the Aß peptide with the Wnt signaling cascade in Drosophila models of Alzheimer's disease. Mol Brain. 2014 Nov 12;7(1):81. PMID: 25387847.

From the abstract: "... Our data confirm that the life span is a useful readout of Aß42 induced neurotoxicity in Drosophila; the neuromuscular junction seems however not to be an appropriate model to study AD in flies. Additionally, our results challenge the hypothesis that Wnt signaling might be implicated in Aß42 toxicity and might serve as a drug target against AD."

Wednesday, November 12, 2014

Review--neurotransmitter release in mammals and flies--relevance to neurodegenerative disease

Davis GW, Müller M. Homeostatic Control of Presynaptic Neurotransmitter Release. Annu Rev Physiol. 2014 Nov 5. PMID: 25386989.

From the abstract: "This review focuses on the homeostatic modulation of presynaptic neurotransmitter release ... we highlight criteria that can be used to define a process as being under homeostatic control. Next, we review the remarkable conservation of presynaptic homeostasis at the Drosophila, mouse, and human neuromuscular junctions ... We then highlight recent progress identifying cellular and molecular mechanisms. We conclude by reviewing emerging parallels between the mechanisms of homeostatic signaling and genetic links to neurological disease."

Drosophila accessory gland as system for study of prostate cancer

Ito S, Ueda T, Ueno A, Nakagawa H, Taniguchi H, Kayukawa N, Miki T. A genetic screen in Drosophila for regulators of human prostate cancer progression. Biochem Biophys Res Commun. 2014 Sep 5;451(4):548-55. PMID: 25117438.

From the abstract: "... identified three genes that promoted growth and migration of secondary cells in the accessory gland. The human homologues of these candidate genes - MRGBP, CNPY2, and MEP1A - were found to be expressed in human prostate cancer model cells and to promote replication and invasiveness in these cells."

Fly study suggests a link between Huntingtin protein and autophagy

Ochaba J, Lukacsovich T, Csikos G, Zheng S, Margulis J, Salazar L, Mao K, Lau AL, Yeung SY, Humbert S, Saudou F, Klionsky DJ, Finkbeiner S, Zeitlin SO, Marsh JL, Housman DE, Thompson LM, Steffan JS. Potential function for the Huntingtin protein as a scaffold for selective autophagy. Proc Natl Acad Sci U S A. 2014 Nov 10. pii: 201420103. PMID: 25385587.

Tuesday, November 11, 2014

Review--Myosin in model systems and links to disease

Lee CF, Melkani GC, Bernstein SI. The UNC-45 Myosin Chaperone: From Worms to Flies to Vertebrates. Int Rev Cell Mol Biol. 2014;313:103-44. PMID: 25376491.

From the abstract: "UNC-45 (uncoordinated mutant number 45) is a UCS (UNC-45, CRO1, She4p) domain protein that is critical for myosin stability and function. It likely aides in folding myosin during cellular differentiation and maintenance, and protects myosin from denaturation during stress. ... we provide insights into UNC-45 functions, its potential mechanism of action, and its roles in human disease."

FlyRNAi: in vivo RNAi screen related to ALS

FlyRNAi: in vivo RNAi screen related to ALS: Deivasigamani S, Verma HK, Ueda R, Ratnaparkhi A, Ratnaparkhi GS. A genetic screen identifies Tor as an interactor of VAPB in a Drosophila m...

Neurodegenerative & neuromuscular disease-related studies--recent reports

Luan Z, Reddig K, Li HS. Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration. Exp Neurol. 2014 Nov;261:791-801. doi: 10.1016/j.expneurol.2014.08.025. Epub 2014 PMID: 25205229; PMCID: PMC4194232.

Rosenbaum EE, Vasiljevic E, Cleland SC, Flores C, Colley NJ. The Gos28 SNARE Mediates Intra-Golgi Transport of Rhodopsin and is Required for Photoreceptor Survival. J Biol Chem. 2014 Sep 26. PMID: 25261468.

Barclay SS, Tamura T, Ito H, Fujita K, Tagawa K, Shimamura T, Katsuta A, Shiwaku H, Sone M, Imoto S, Miyano S, Okazawa H. Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1. Hum Mol Genet. 2014 Mar 1;23(5):1345-64. doi: 10.1093/hmg/ddt524. PMID: 24179173.  From the abstract: "In this study, we performed a systematic in vivo screen of all available Drosophila melanogaster homolog DNA repair genes, and we tested the effect of their overexpression on lifespan and developmental viability in Spinocerebellar Ataxia Type 1 (SCA1) Drosophila models expressing human mutant Ataxin-1 (Atxn1)."

Xu S, Wilf R, Menon T, Panikker P, Sarthi J, Elefant F. Epigenetic Control of Learning and Memory in Drosophila by Tip60 HAT Action. Genetics. 2014 Oct 17. PMID: 25326235. From the abstract: "Disruption of epigenetic gene control mechanisms in the brain causes significant cognitive impairment that is a debilitating hallmark of most neurodegenerative disorders including Alzheimer's disease (AD). ... Here, we investigate an epigenetic role for the HAT Tip60 in learning and memory formation using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. ... we find that both learning and immediate recall memory deficits that occur under AD associated amyloid precursor protein (APP) induced neurodegenerative conditions can be effectively rescued by increasing Tip60 HAT levels specifically in the MB. ..."

Stepto A, Gallo JM, Shaw CE, Hirth F. Modelling C9ORF72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol. 2014 Mar;127(3):377-89. PMID: 24366528. From the abstract of this review: "... studies using patient-derived cells, as well as Drosophila and zebrafish models overexpressing disease-related hexanucleotide expansions, can cause repeat length-dependent formation of RNA foci, which directly and progressively correlate with cellular toxicity. ..."

Zwarts L, Van Eijs F, Callaerts P. Glia in Drosophila behavior. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2014 Oct 22. PMID: 25336160. From the abstract: "... We here summarize recent work describing the role of glia in normal behavior and in Drosophila models for neurological and behavioral disorders."

Fly study relevant to Menkes and Wilson diseases

Hwang JE, de Bruyne M, Warr CG, Burke R. Copper overload and deficiency both adversely affect the central nervous system of Drosophila. Metallomics. 2014 Oct 17. PMID: 25322772.

From the abstract: "The human copper homeostasis disorders Menkes and Wilson disease both have severe neurological symptoms. Menkes is a copper deficiency disorder whereas Wilson disease patients suffer from copper toxicity, indicating that tight control of neuronal copper levels is essential for proper nervous system development and function. Here we examine the consequences of neuronal copper deficiency and excess in the Drosophila melanogaster nervous system, using targeted manipulation of the copper uptake genes Ctr1A and Ctr1B and efflux gene ATP7 in combination with altered dietary copper levels. ... We conclude that both copper overload and excess have detrimental effects on Drosophila neuronal function, reducing overall fly viability as well as impacting on a specific neuropeptide pathway."

Review relevant to Dscam proteins and Down's syndrome

Montesinos ML. Roles for DSCAM and DSCAML1 in central nervous system development and disease. Adv Neurobiol. 2014;8:249-70. PMID: 25300140.

From the abstract: "... In Drosophila, Dscam proteins are involved in neuronal wiring, while in vertebrates, the role of these cell adhesion molecules in neurogenesis, dendritogenesis, axonal outgrowth, synaptogenesis, and synaptic plasticity is only just beginning to be understood. In this chapter, we will review the functions ascribed to the two paralogous proteins found in humans, DSCAM and DSCAML1 (DSCAM-like 1), based on findings in knockout mice. The signaling pathways downstream of DSCAM activation and the role of DSCAM miss-expression in disease will be also discussed, particularly with regard to the intellectual disability in Down's syndrome."

FlyRNAi: Genome-wide RNAi screen related to Parkinson's dis...

FlyRNAi: Genome-wide RNAi screen related to Parkinson's dis...: Ivatt RM, Sanchez-Martinez A, Godena VK, Brown S, Ziviani E, Whitworth AJ. Genome-wide RNAi screen identifies the Parkinson disease GWAS ris...