Friday, August 31, 2018

Results from a fly genetic screen implicate a long non-coding RNA in Charcot-Marie-Tooth disease

Muraoka Y, Nakamura A, Tanaka R, Suda K, Azuma Y, Kushimura Y, Piccolo LL, Yoshida H, Mizuta I, Tokuda T, Mizuno T, Nakagawa M, Yamaguchi M. Genetic screening of the genes interacting with Drosophila FIG4 identified a novel link between CMT-causing gene and long noncoding RNAs. Exp Neurol. 2018 Aug 27. pii: S0014-4886(18)30377-7. PMID: 30165075.

From the abstract: "Neuron-specific knockdown of the dFIG4 gene, a Drosophila homologue of human FIG4 and one of the causative genes for Charcot-Marie-Tooth disease (CMT), reduces the locomotive abilities of adult flies, as well as causing defects at neuromuscular junctions ... By genetic screening, we detected 9 and 15 chromosomal regions whose deletions either suppressed or enhanced the rough eye phenotype induced by the dFIG4 knockdown. By further genetic screening ... we identified the gene CR18854 that suppressed the rough eye phenotype and the loss-of-cone cell phenotype. The CR18854 gene encodes a long non-coding RNA (lncRNA) consisting of 2566 bases. ... We also obtained data indicating genetic interaction between CR18854 and Cabeza, a Drosophila homologue of human FUS, which is one of the causing genes for amyotrophic lateral sclerosis (ALS). These results suggest that lncRNAs such as CR18854 and hsrω are involved in a common pathway in CMT and ALS pathogenesis."

Wednesday, August 29, 2018

New fly model: Cigarette smoke-induced COPD

Prange R, Thiedmann M, Bhandari A, Mishra N, Sinha A, Häsler R, Rosenstiel P, Uliczka K, Wagner C, Yildirim AÖ, Fink C, Roeder T. A Drosophila model of cigarette smoke induced COPD identifies Nrf2 signaling as an expedient target for intervention. Aging (Albany NY). 2018 Aug 27. PMID: 30153653.

From the abstract: "Chronic obstructive pulmonary disease (COPD) is among the most important causes of death. ... Here, we developed a simple cigarette smoke induced Drosophila model of COPD based on chronic cigarette smoke exposure that recapitulates major pathological hallmarks of the disease and thus can be used to investigate new therapeutic strategies. ... the Drosophila COPD model recapitulates many major hallmarks of COPD and it is highly useful to evaluate the potential of alternative therapeutic strategies."

TREK-1 potassium channel in heart health: From Drosophila genetic screen to mammalian follow-up studies

Abraham DM, Lee TE, Watson LJ, Mao L, Chandok GS, Wang HG, Frangakis S, Pitt GS, Shah SH, Wolf MJ, Rockman HA. The two-pore-domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction. J Clin Invest. 2018 Aug 28. PMID: 30153110.

From the abstract: "Cardiac two pore domain potassium channels (K2P) exist in organisms from Drosophila to humans ... We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critical to cardiac function. Mice lacking an ortholog of sandman, TWIK related potassium channel (TREK-1 or Kcnk2), exhibit exaggerated pressure overload induced concentric hypertrophy and alterations in fetal gene expression ... These findings indicate a central role for cardiac fibroblast TREK-1 in the pathogenesis of pressure overload-induced cardiac dysfunction and serve as a conceptual basis for its inhibition for as a potential therapy."

Tuesday, August 28, 2018

Drosophila, diabetes, and kidney disease

Rani L, Gautam NK. Drosophila renal system as an in-vivo tool for target identification and screening of potential therapeutics for the diabetic nephropathy. Curr Drug Targets. 2018 Aug 7. PMID: 30088447.

From the abstract: "... This review provides evidence for the use of Drosophila renal system as an in-vivo tool for identifying drug target against the disease. ... It also illustrates the use of Drosophila based tools for pre-screening of a potential drug for the disease."

Expression of human disease alleles in Drosophila used to study cellular mechanisms of diseases associated with polyglutamine expansion

Vu A, Humphries T, Vogel S, Haberman A. Polyglutamine repeat proteins disrupt actin structure in Drosophila photoreceptors. Mol Cell Neurosci. 2018 Aug 24. PMID: 30149064.

The abstract: "Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites. We show this actin regulatory pathway works through the small G protein Rac and the actin nucleating protein Form3. We also find that Form3 has additional functions in photoreceptors, and that loss of Form3 results in the specification of extra photoreceptors in the eye."

Review: Using Drosophila to help interpret genome-wide association study (GWAS) data related to Alzheimer's Disease

Dourlen P, Chapuis J, Lambert JC. Using High-Throughput Animal or Cell-Based Models to Functionally Characterize GWAS Signals. Curr Genet Med Rep. 2018;6(3):107-115. PMID: 30147999; PMCID: PMC6096908.

From the abstract: "... genome-wide association studies (GWASs) constituted a breakthrough in our understanding of the genetic architecture of multifactorial diseases. For Alzheimer's disease (AD), more than 20 risk loci have been identified. However, we are now facing three new challenges: (i) identifying the functional SNP or SNPs in each locus, (ii) identifying the causal gene(s) in each locus, and (iii) understanding these genes' contribution to pathogenesis. ... To address these issues ... a number of high-throughput strategies have been implemented ... Here, we review high-throughput screening, high-content screening, and the use of the Drosophila model (primarily with reference to AD)."

Monday, August 27, 2018

Review: Omega-Class GSTs in Neurodegenerative Diseases

Kim Y, Cha SJ, Choi HJ, Kim K. Omega Class Glutathione S-Transferase: Antioxidant Enzyme in Pathogenesis of Neurodegenerative Diseases. Oxid Med Cell Longev. 2017;2017:5049532. PMID: 29435097; PMCID: PMC5757135.

From the abstract: "The omega class glutathione S-transferases (GSTOs) are multifunctional enzymes involved in cellular defense and have distinct structural and functional characteristics, which differ from those of other GSTs. ... In this review, we briefly introduce recent studies and summarize the novel biological functions and mechanisms underpinning neuroprotective effects of GstOs in Drosophila."

Fly Study Points to Bacterial Regulation of Acetate as Factor in Vibrio cholera virulence

Liimatta K, Flaherty E, Ro G, Nguyen DK, Prado C, Purdy AE. A putative acetylation system in Vibrio cholerae modulates virulence in arthropod hosts. Appl Environ Microbiol. 2018 Aug 24. PMID: 30143508.

From the abstract: "Acetylation is a broadly conserved mechanism of covalently modifying the proteome to precisely control protein activity. In bacteria, central metabolic enzymes and regulatory proteins, including those involved in virulence, can be targeted for acetylation. In this study, we directly link a putative acetylation system to metabolite-dependent virulence in the pathogen Vibrio cholerae ... The Drosophila model of Vibrio cholerae infection has revealed that bacterial regulation of acetate and other small metabolites from within the fly gastrointestinal tract is crucial to its virulence. Here, we demonstrate that genes that may modify the proteome of V. cholerae affect virulence towards Drosophila ... These findings further highlight the many layers of regulation that tune bacterial metabolism to alter the trajectory of interactions between bacteria and their hosts."

Wednesday, August 22, 2018

Review of fly research in the area of Parkinson's disease

Fatima A, Jyoti S, Siddique YH. Models of Parkinson's disease with special emphasis on Drosophila melanogaster. CNS Neurol Disord Drug Targets. 2018 Aug 20. PMID: 30129420.

Abstract: "Parkinson's disease is the second most common neurodegenerative disorder affecting more than 1% of the population average 60. The majority of PD cases are sporadic and are probably caused by a combination of risk factors but 5-10% of the PD cases are familial. Due to the high degree of gene conservation between humans, mice and insects using animal model system is a valuable approach to further elucidate the roles of the genes in PD. The present review highlights the models use to study PD symptoms with special emphasis on Drosophila."

Friday, August 17, 2018

Review of fly research in the area of Huntington's Disease

Rosas-Arellano A, Estrada-Mondragón A, Piña R, Mantellero CA, Castro MA. The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington's Disease. Int J Mol Sci. 2018 Aug 14;19(8). PMID: 30110961.

The abstract: "The average life expectancy for humans has increased over the last years. However, the quality of the later stages of life is low and is considered a public health issue of global importance. Late adulthood and the transition into the later stage of life occasionally leads to neurodegenerative diseases that selectively affect different types of neurons and brain regions, producing motor dysfunctions, cognitive impairment, and psychiatric disorders that are progressive, irreversible, without remission periods, and incurable. Huntington's disease (HD) is a common neurodegenerative disorder. In the 25 years since the mutation of the huntingtin (HTT) gene was identified as the molecule responsible for this neural disorder, a variety of animal models, including the fruit fly, have been used to study the disease. Here, we review recent research that used Drosophila as an experimental tool for improving knowledge about the molecular and cellular mechanisms underpinning HD."

Tuesday, August 14, 2018

Preprint: "A Drosophila Model for Behavioral Sleep Modification"

BioRxiv Preprint: "A Drosophila Model for Behavioral Sleep Modification"
Samuel J Belfer, Alexander G Bashaw, Michael L Perlis, Matthew S Kayser



From the abstract: "Insomnia is the most common sleep disorder among adults, especially affecting individuals of advanced age or with neurodegenerative disease. ... Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first-line treatment for insomnia ... Despite the well-documented efficacy of CBT-I, little is known regarding how CBT-I works at a cellular and molecular level ... Here, guided by human behavioral sleep therapies, we developed a Drosophila model for behavioral modification of sleep. ... We apply this sleep opportunity restriction paradigm to aging and Alzheimer's disease fly models, and find that sleep impairments in these models are reversible with sleep restriction ... This work establishes a model to investigate the neurobiological basis of CBT-I, and provides a platform that can be exploited towards novel treatment targets for insomnia."