Review -- Drosophila models for the study of motor neuron diseases

Walters R, Manion J, Neely GG. Dissecting Motor Neuron Disease With Drosophila melanogaster. Front Neurosci. 2019 Apr 12;13:331. doi: 10.3389/fnins.2019.00331. PMID: 31031583; PMCID: PMC6473072.

Abstract: "Motor Neuron Disease (MND) typically affects patients during the later stages of life, and thus, MND is having an increasingly devastating impact on diagnosed individuals, their families and society. The umbrella term MND refers to diseases which cause the progressive loss of upper and/or lower motor neurons and a subsequent decrease in motor ability such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). The study of these diseases is complex and has recently involved the use of genome-wide association studies (GWAS). However, in the case of MND, it has been difficult to identify the complex genetics involved in subtypes, and functional investigation of new candidate disease genes is warranted. Drosophila is a powerful model for addressing these complex diseases. The UAS/Gal4/Gal80 system allows for the upregulation of Drosophila genes, the "knockdown" of genes and the ectopic expression of human genes or mutations in a tissue-specific manner; often resulting in Drosophila models which exhibit typical MND disease pathologies. These can then be further interrogated to identify disease-modifying genes or mutations and disease pathways. This review will discuss two common MNDs and the current Drosophila models which are being used to research their genetic basis and the different pathologies of MND."

Preprint: Researchers compare among 14 fly models of Spinal Muscular Atrophy (SMA)

Posted November 2018 on the BioRxiv preprint server:

Ashlyn M. Spring, Amanda C. Raimer, Christine D. Hamilton, Michela J. Schillinger, A. Gregory Matera
Comprehensive modeling of Spinal Muscular Atrophy in Drosophila melanogaster
https://www.biorxiv.org/content/10.1101/394908v3

From the preprint abstract: "Spinal muscular atrophy (SMA) is a neurodegenerative disorder that affects motor neurons, primarily in young children. ... A systematic analysis of SMA-related phenotypes in the context of moderate alleles that more closely mimic the genetics of SMA has not been performed in the fly, leading to debate over the validity and translational value of this model. We therefore examined fourteen Drosophila lines expressing SMA patient-derived missense mutations in Smn ... on the basis of organismal viability and longevity, locomotor function, neuromuscular junction structure, and muscle health. In all cases, we observed phenotypes similar to those of SMA patients, including progressive loss of adult motor function. The severity of these defects is variable, and forms a broad spectrum across the fourteen lines examined, recapitulating the full range of phenotypic severity observed in human SMA. ... The results provide direct evidence that SMA-related locomotor decline can be reproduced in the fly and support the use of patient-derived SMN missense mutations as a comprehensive system for modeling SMA."

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.

Catching up (or at least, beginning to) on neurodegenerative disease-related fly papers

Reviews

Foriel S, Willems P, Smeitink J, Schenck A, Beyrath J. Mitochondrial diseases: Drosophila melanogaster as a model to evaluate potential therapeutics. Int J Biochem Cell Biol. 2015 Jun;63:60-5. PMID: 25666557.

Repalli J. Translocator protein (TSPO) role in aging and Alzheimer's disease. Curr Aging Sci. 2014;7(3):168-75. PMID: 25495567; PMCID: PMC4435228.

Research papers

Wu K, Liu J, Zhuang N, Wang T. UCP4A protects against mitochondrial dysfunction and degeneration in pink1/parkin models of Parkinson's disease. FASEB J. 2014 Dec;28(12):5111-21. PMID: 25145627.

Vorobyeva AG, Lee R, Miller S, Longen C, Sharoni M, Kandelwal PJ, Kim FJ, Marenda DR, Saunders AJ. Cyclopamine modulates γ-secretase-mediated cleavage of amyloid precursor protein by altering its subcellular trafficking and lysosomal degradation. J Biol Chem. 2014 Nov 28;289(48):33258-74. PMID: 25281744; PMCID: PMC4246084.

Butzlaff M, Hannan SB, Karsten P, Lenz S, Ng J, Voßfeldt H, Prüßing K, Pflanz R, Schulz JB, Rasse T, Voigt A. Impaired retrograde transport by the Dynein/Dynactin complex contributes to Tau-induced toxicity. Hum Mol Genet. 2015 Jul 1;24(13):3623-37. PMID: 25794683.

Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scott M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015 Feb;138(Pt 2):293-310. PMID: 25497877; PMCID: PMC4306822. ---See also comment and reply.

Doll CA, Broadie K. Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory. Development. 2015 Apr 1;142(7):1346-56. PMID: 25804740; PMCID: PMC4378248.

Sanhueza M, Chai A, Smith C, McCray BA, Simpson TI, Taylor JP, Pennetta G. Network analyses reveal novel aspects of ALS pathogenesis. PLoS Genet. 2015 Mar 31;11(3):e1005107. PMID: 25826266; PMCID: PMC4380362.

Dalui S, Bhattacharyya A. Herbicide paraquat induces sex-specific variation of neuroinflammation and neurodegeneration in Drosophila melanogaster. Indian J Biochem Biophys. 2014 Dec;51(6):567-73. PubMed PMID: 25823231.

Jimenez-Sanchez M, Lam W, Hannus M, Sönnichsen B, Imarisio S, Fleming A, Tarditi A, Menzies F, Ed Dami T, Xu C, Gonzalez-Couto E, Lazzeroni G, Heitz F, Diamanti D, Massai L, Satagopam VP, Marconi G, Caramelli C, Nencini A, Andreini
M, Sardone GL, Caradonna NP, Porcari V, Scali C, Schneider R, Pollio G, O'Kane CJ, Caricasole A, Rubinsztein DC. siRNA screen identifies QPCT as a draggable target for Huntington's disease. Nat Chem Biol. 2015 May;11(5):347-54. PMID: 25848931; PMCID: PMC4696152.

Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015 Jan 15;160(1-2):177-90. PMID: 25594180; PMCID: PMC4377295.

Wen X, Tan W, Westergard T, Krishnamurthy K, Markandaiah SS, Shi Y, Lin S, Shneider NA, Monaghan J, Pandey UB, Pasinelli P, Ichida JK, Trotti D. Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death. Neuron. 2014 Dec 17;84(6):1213-25. PMID: 25521377; PMCID: PMC4632245.

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 Huntington protein as a scaffold for selective autophagy. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16889-94. PMID: 25385587; PMCID: PMC4250109.

Wade AR, Elliott CJ. Could the detection of visual disturbances associated with Parkinson's disease genes in flies lead to new treatments for the disease? Neurodegener Dis Manag. 2014;4(4):291-3. PMID: 25313984.

Yin G, Lopes da Fonseca T, Eisbach SE, Anduaga AM, Breda C, Orcellet ML, Szegő ÉM, Guerreiro P, Lázaro DF, Braus GH, Fernandez CO, Griesinger C, Becker S, Goody RS, Itzen A, Giorgini F, Outeiro TF, Zweckstetter M. α-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner. Neurobiol Dis. 2014 Oct;70:149-61. PMID: 24983211.

Kim Y, Park H, Nah J, Moon S, Lee W, Hong SH, Kam TI, Jung YK. Essential role of POLDIP2 in Tau aggregation and neurotoxicity via autophagy/proteasome inhibition. Biochem Biophys Res Commun. 2015 Jun 26;462(2):112-8. PMID: 25930997.

Scaramuzzino C, Casci I, Parodi S, Lievens PM, Polanco MJ, Milioto C, Chivet M, Monaghan J, Mishra A, Badders N, Aggarwal T, Grunseich C, Sambataro F, Basso M, Fackelmayer FO, Taylor JP, Pandey UB, Pennuto M. Protein arginine
methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy. Neuron. 2015 Jan 7;85(1):88-100. PMID: 25569348; PMCID: PMC4305189.

More catching up -- fly models helping to reveal new insights into neurodegenertive diseases

Parkinson's Disease

Reviews

Gaki GS, Papavassiliou AG. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease. Neuromolecular Med. 2014 Jun;16(2):217-30. PMID: 24522549.

Deng H, Yuan L. Genetic variants and animal models in SNCA and Parkinson disease. Ageing Res Rev. 2014 May;15:161-76. PMID: 24768741.

Research reports

Büttner S, Broeskamp F, Sommer C, Markaki M, Habernig L, Alavian-Ghavanini A, Carmona-Gutierrez D, Eisenberg T, Michael E, Kroemer G, Tavernarakis N, Sigrist SJ, Madeo F. Spermidine protects against α-synuclein neurotoxicity. Cell Cycle. 2014;13(24):3903-8. PMID: 25483063.

Siddique YH, Naz F, Jyoti S, Fatima A, Khanam S, Rahul, Ali F, Mujtaba SF, Faisal M. Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson's Disease. Parkinsons Dis. 2014;2014:262058. PMID: 25538856; PMCID: PMC4265550.

Roy B, Jackson GR. Interactions between Tau and α-synuclein augment neurotoxicity in a Drosophila model of Parkinson's disease. Hum Mol Genet. 2014 Jun 1;23(11):3008-23. PMID:
24430504; PMCID: PMC4014195. From the abstract: "Clinical and pathological studies have suggested considerable overlap between tauopathies and synucleinopathies. Several genome-wide association studies have identified alpha-Synuclein (SNCA) and Tau (MAPT) polymorphisms as common risk factors for sporadic Parkinson's disease (PD). However, the mechanisms by which subtle variations in the expression of wild-type SNCA and MAPT influence risk for PD and the underlying cellular events that effect neurotoxicity remain unclear. To examine causes of neurotoxicity associated with the α-Syn/Tau interaction, we used the fruit fly as a model. ... "

Angeles DC, Ho P, Chua LL, Wang C, Yap YW, Ng C, Zhou Zd, Lim KL, Wszolek ZK, Wang HY, Tan EK. Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila. Hum Mol Genet. 2014 Jun 15;23(12):3157-65. PMID: 24459295; PMCID: PMC4030771.

Alzheimer's Disease and Tauopathies

Wacker J, Rönicke R, Westermann M, Wulff M, Reymann KG, Dobson CM, Horn U, Crowther DC, Luheshi LM, Fändrich M. Oligomer-targeting with a conformational antibody fragment promotes toxicity in Aβ-expressing flies. Acta Neuropathol Commun. 2014 Apr 11;2:43. PMID: 24725347; PMCID: PMC4029271.

Papanikolopoulou K, Skoulakis EM. Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila. Hum Mol Genet. 2015 Apr 1;24(7):2065-77. doi: 10.1093/hmg/ddu726. PMID: 25524708.

Santa-Maria I, Alaniz ME, Renwick N, Cela C, Fulga TA, Van Vactor D, Tuschl T, Clark LN, Shelanski ML, McCabe BD, Crary JF. Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau. J Clin Invest. 2015 Feb;125(2):681-6. PubMed PMID: 25574843; PMCID: PMC4319412.

Huntington's Disease

Maheshwari M, Bhutani S, Das A, Mukherjee R, Sharma A, Kino Y, Nukina N, Jana NR. Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease. Hum Mol Genet. 2014 May 15;23(10):2737-51. PMID: 24381308.

Lu XH, Mattis VB, Wang N, Al-Ramahi I, van den Berg N, Fratantoni SA, Waldvogel H, Greiner E, Osmand A, Elzein K, Xiao J, Dijkstra S, de Pril R, Vinters HV, Faull R, Signer E, Kwak S, Marugan JJ, Botas J, Fischer DF, Svendsen CN, Munoz-Sanjuan I, Yang XW. Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington's disease. Sci Transl Med. 2014 Dec 24;6(268):268ra178. PMID: 25540325.

Vittori A, Breda C, Repici M, Orth M, Roos RA, Outeiro TF, Giorgini F, Hollox EJ; REGISTRY investigators of the European Huntington's Disease Network. Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease. Hum Mol Genet. 2014 Jun 15;23(12):3129-37. PMID: 24452335; PMCID: PMC4030768.

ALS

King IN, Yartseva V, Salas D, Kumar A, Heidersbach A, Ando DM, Stallings NR, Elliott JL, Srivastava D, Ivey KN. The RNA-binding protein TDP-43 selectively disrupts microRNA-1/206 incorporation into the RNA-induced silencing complex. J Biol Chem. 2014 May 16;289(20):14263-71. PMID: 24719334; PMCID: PMC4022891.

SMA

Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015 Feb;138(Pt 2):293-310. PMID: 25497877; PMCID: PMC4306822.

Additional relevant to neurodegenerative disease

Manayi A, Saeidnia S, Gohari AR, Abdollahi M. Methods for the discovery of new anti-aging products--targeted approaches. Expert Opin Drug Discov. 2014 Apr;9(4):383-405. PMID: 24494592.

Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015 Jan 15;160(1-2):177-90. PMID: 25594180; PMCID: PMC4377295. From the abstract: "Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated in neurodegenerative disease. Here, we find that a key consequence of ROS and neuronal mitochondrial dysfunction is the accumulation of lipid droplets (LD) in glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP) activity in neurons leading to LD accumulation in glia ... "

Flies & SMA

Praveen K, Wen Y, Gray KM, Noto JJ, Patlolla AR, Van Duyne GD, Matera AG. SMA-causing missense mutations in survival motor neuron (Smn) display a wide range of phenotypes when modeled in Drosophila. PLoS Genet. 2014 Aug 21;10(8):e1004489. PMID: 25144193; PMCID: PMC4140637.

New fly studies and review related to neurodegenerative diseases

Parkinson's-related studies:

Thomas RE, Andrews LA, Burman JL, Lin WY, Pallanck LJ. PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix. PLoS Genet. 2014 May 29;10(5):e1004279. PMID: 24874806.

Chen AY, Xia S, Wilburn P, Tully T. Olfactory Deficits in an Alpha-Synuclein Fly Model of Parkinson's Disease. PLoS One. 2014 May 30;9(5):e97758. PMID: 24879013.

Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell. 2014 Apr 10;157(2):472-85. PMID: 24725412.

Cornelissen T, Haddad D, Wauters F, Van Humbeeck C, Mandemakers W, Koentjoro B, Sue C, Gevaert K, De Strooper B, Verstreken P, Vandenberghe W. The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy. Hum Mol Genet. 2014 May 22. PMID: 24852371.

Siddique YH, Naz F, Jyoti S. Effect of curcumin on lifespan, activity pattern, oxidative stress, and apoptosis in the brains of transgenic Drosophila model of Parkinson's disease. Biomed Res Int. 2014;2014:606928. PMID: 24860828; PubMed Central PMCID: PMC4016861.

Shukla AK, Pragya P, Chaouhan HS, Tiwari AK, Patel DK, Abdin MZ, Chowdhuri DK. Heat Shock Protein-70 (Hsp-70) Suppresses Paraquat-Induced Neurodegeneration by Inhibiting JNK and Caspase-3 Activation in Drosophila Model of Parkinson's Disease. PLoS One. 2014 Jun 2;9(6):e98886. PMID: 24887138.

Knight AL, Yan X, Hamamichi S, Ajjuri RR, Mazzulli JR, Zhang MW, Daigle JG, Zhang S, Borom AR, Roberts LR, Lee SK, DeLeon SM, Viollet-Djelassi C, Krainc D, O'Donnell JM, Caldwell KA, Caldwell GA. The Glycolytic Enzyme, GPI, Is a Functionally Conserved Modifier of Dopaminergic Neurodegeneration in Parkinson's Models. Cell Metab. 2014 May 28. PMID: 24882066.

ALS-related studies:

Hans F, Fiesel FC, Strong JC, Jäckel S, Rasse TM, Geisler S, Springer W, Schulz JB, Voigt A, Kahle PJ. UBE2E ubiquitin-conjugating enzymes and ubiquitin isopeptidase Y regulate TDP-43 ubiquitinylation. J Biol Chem. 2014 May 13. PMID: 24825905.

Salado IG, Redondo M, Bello ML, Perez C, Liachko NF, Kraemer BC, Miguel L, Lecourtois M, Gil C, Martinez A, Perez DI. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J Med Chem. 2014 Mar 27;57(6):2755-72. PMID: 24592867; PubMed Central PMCID: PMC3969104.

Huntington's-related studies:

O'Rourke JG, Gareau JR, Ochaba J, Song W, Raskó T, Reverter D, Lee J, Monteys AM, Pallos J, Mee L, Vashishtha M, Apostol BL, Nicholson TP, Illes K, Zhu YZ, Dasso M, Bates GP, Difiglia M, Davidson B, Wanker EE, Marsh JL, Lima CD, Steffan JS, Thompson LM. SUMO-2 and PIAS1 modulate insoluble mutant huntingtin protein accumulation. Cell Rep. 2013 Jul 25;4(2):362-75. PMID: 23871671; PubMed Central PMCID: PMC3931302.

SCA-related study:

Jia DD, Zhang L, Chen Z, Wang CR, Huang FZ, Duan RH, Xia K, Tang BS, Jiang H. Lithium chloride alleviates neurodegeneration partly by inhibiting activity of GSK3β in a SCA3 Drosophila model. Cerebellum. 2013 Dec;12(6):892-901. PMID: 23812869.

SMA-related study:

Wishart TM, Mutsaers CA, Riessland M, Reimer MM, Hunter G, Hannam ML, Eaton SL, Fuller HR, Roche SL, Somers E, Morse R, Young PJ, Lamont DJ, Hammerschmidt M, Joshi A, Hohenstein P, Morris GE, Parson SH, Skehel PA, Becker T, Robinson IM, Becker CG, Wirth B, Gillingwater TH. Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy. J Clin Invest. 2014 Apr 1;124(4):1821-34.  PMID: 24590288; PubMed Central PMCID: PMC3973095.

Review:

Lee S, Bang SM, Lee JW, Cho KS. Evaluation of Traditional Medicines for Neurodegenerative Diseases Using Drosophila Models. Evid Based Complement Alternat Med. 2014;2014:967462. Review. PubMed PMID: 24790636; PubMed Central PMCID: PMC3984789.

New review--Drosophila studies and neurodegenerative diseases

Charng WL, Yamamoto S, Bellen HJ. Shared mechanisms between Drosophila peripheral nervous system development and human neurodegenerative diseases. Curr Opin Neurobiol. 2014 Apr 21;27C:158-164. PMID: 24762652.

Fly study related to SMA

Borg R, Cauchi RJ. The gemin associates of survival motor neuron are required for motor function in Drosophila. PLoS One. 2013 Dec 31;8(12):e83878. PMID: 24391840; PMCID: PMC3877121.

Flies & muscle atrophy--recent review

Piccirillo R, Demontis F, Perrimon N, Goldberg AL. Mechanisms of muscle growth and atrophy in mammals and Drosophila. Dev Dyn. 2013 Aug 29. PMID: 24038488.

Fly studies relevant to spinal muscular atrophy

Garcia EL, Lu Z, Meers MP, Praveen K, Matera AG. Developmental arrest of Drosophila survival motor neuron (Smn) mutants accounts for differences in expression of minor intron-containing genes. RNA. 2013 Sep 4. PMID: 24006466.

Sen A, Dimlich DN, Guruharsha KG, Kankel MW, Hori K, Yokokura T, Brachat S, Richardson D, Loureiro J, Sivasankaran R, Curtis D, Davidow LS, Rubin LL, Hart AC, Van Vactor D, Artavanis-Tsakonas S. Genetic circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):E2371-80. PMID: 23757500; PMCID: PMC3696827.

Genetic modifiers related to spinal muscular atrophy. Recent report.

Sen A, Dimlich DN, Guruharsha KG, Kankel MW, Hori K, Yokokura T, Brachat S, Richardson D, Loureiro J, Sivasankaran R, Curtis D, Davidow LS, Rubin LL, Hart AC, Van Vactor D, Artavanis-Tsakonas S. Genetic circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy. Proc Natl Acad Sci U S A. 2013 Jun 11. PMID: 23757500.

From the abstract: "... we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog."

Flies & Worms & Spinal Myscular Atrophy. Recent report.

Dimitriadi M, Kye MJ, Kalloo G, Yersak JM, Sahin M, Hart AC. The Neuroprotective Drug Riluzole Acts via Small Conductance Ca2+-Activated K+ Channels to Ameliorate Defects in Spinal Muscular Atrophy Models. J Neurosci. 2013 Apr 10;33(15):6557-62. PubMed PMID: 23575853.

From the abstract: "... parallel genetic screens were undertaken in Drosophila and Caenorhabditis elegans SMA models to identify modifiers of the SMN loss of function phenotypes ... We examine here the impact of riluzole in two different SMA models. ... We propose that riluzole improves motor neuron function by acting on SK channels and suggest that SK channels may be important therapeutic targets for SMA patients."

Uncoupling of snRNPs from SMA. Recent report.

This paper is now freely available in PubMed Central.

Praveen K, Wen Y, Matera AG. A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects. Cell Rep. 2012 Jun 28;1(6):624-31. PMID: 22813737; PMCID: PMC3405901.

From the abstract: "These findings have major implications for SMA etiology because they show that SMN's role in snRNP biogenesis can be uncoupled from the organismal viability and locomotor defects."

See also this posted paper on splicing & SMA.
Or all blog posts on SMA.

X-linked Infantile Spinal Muscular Atrophy. Fly model. Recent report.

Liu HY, Pfleger CM. Mutation in e1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment. PLoS One. 2013;8(1):e32835. doi: 10.1371/journal.pone.0032835. Epub 2013 Jan 29. PubMed PMID: 23382794; PubMed Central PMCID: PMC3558519.

Flies and fish contribute to study on SMA. Recent report.

Lotti F, Imlach WL, Saieva L, Beck ES, Hao le T, Li DK, Jiao W, Mentis GZ, Beattie CE, McCabe BD, Pellizzoni L. An SMN-dependent U12 splicing event essential for motor circuit function. Cell. 2012 Oct 12;151(2):440-54. doi: 10.1016/j.cell.2012.09.012. PubMed PMID: 23063131; PubMed Central PMCID: PMC3474596.

Knockdown of SMN in fly neurons and muscles. Recent report.

Loss of SMN1 activity leads to Spinal Muscular Atrophy (SMA). In this study, the fly ortholog of SMN1 was knocked down by RNAi in neurons and muscles.

Timmerman C, Sanyal S. Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster. Brain Res. 2012 Oct 25. doi:pii: S0006-8993(12)01692-7. 10.1016/j.brainres.2012.10.035. PubMed PMID: 23103409.

Fly model of SMA. SMN in Neural Network Activity. Recent Report.

Imlach WL, Beck ES, Choi BJ, Lotti F, Pellizzoni L, McCabe BD. SMN Is Required for Sensory-Motor Circuit Function in Drosophila. Cell. 2012 Oct 12;151(2):427-39. doi: 10.1016/j.cell.2012.09.011. PubMed PMID: 23063130.