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."