Ishikawa K, Nagai Y. Molecular Mechanisms and Future Therapeutics for Spinocerebellar Ataxia Type 31 (SCA31). Neurotherapeutics. 2019 Nov 21. PubMed PMID: 31755042.
From the abstract: "Spinocerebellar ataxia type 31 (SCA31) is one of the autosomal-dominant neurodegenerative disorders that shows progressive cerebellar ataxia as a cardinal symptom. This disease is caused by a 2.5- to 3.8-kb-long complex pentanucleotide repeat containing (TGGAA)n, (TAGAA)n, (TAAAA)n, and (TAAAATAGAA)n in an intron of the gene called BEAN1 (brain expressed, associated with Nedd4). ... To dissect the pathogenesis of (UGGAA)n in SCA31, we generated transgenic fly models of SCA31 by overexpressing SCA31 complex pentanucleotide repeats in Drosophila. We found that the toxicity of (UGGAA)n is length- and expression level-dependent, and it was dampened by co-expressing TDP-43, FUS, and hnRNP A2/B1. ..."
Showing posts with label Spinocerebellar ataxia. Show all posts
Showing posts with label Spinocerebellar ataxia. Show all posts
Wednesday, December 4, 2019
Monday, December 2, 2019
Drosophila model of Spinocerebellar Ataxia type 3 used as part of an effort to identify drug targets for treatment of this ataxia
Ashraf NS, Sutton JR, Yang Y, Ranxhi B, Libohova K, Shaw ED, Barget AJ, Todi SV, Paulson HL, do Carmo Costa M. Druggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia type 3 disease protein. Neurobiol Dis. 2019 Nov 26:104697. PMID: 31783119.
From the abstract: "Spinocerebellar Ataxia type 3 (SCA3, also known as Machado-Joseph disease) is a neurodegenerative disorder ... No preventive treatment is yet available for SCA3. ... Here, we sought to identify genes that modulate ATXN3 levels as potential therapeutic targets in this fatal disorder. We screened a collection of siRNAs targeting 2742 druggable human genes using a cell-based assay ... Among the 33 genes confirmed in secondary assays, 15 were validated in an independent cell model as modulators of pathogenic ATXN3 protein levels. Ten of these genes were then assessed in a Drosophila model of SCA3, and one was confirmed as a key modulator of physiological ATXN3 abundance in SCA3 neuronal progenitor cells. ... Among identified pathways highlighted by this screen, the FBXL3/SCF axis represents a novel molecular pathway that regulates physiological levels of ATXN3 protein."
From the abstract: "Spinocerebellar Ataxia type 3 (SCA3, also known as Machado-Joseph disease) is a neurodegenerative disorder ... No preventive treatment is yet available for SCA3. ... Here, we sought to identify genes that modulate ATXN3 levels as potential therapeutic targets in this fatal disorder. We screened a collection of siRNAs targeting 2742 druggable human genes using a cell-based assay ... Among the 33 genes confirmed in secondary assays, 15 were validated in an independent cell model as modulators of pathogenic ATXN3 protein levels. Ten of these genes were then assessed in a Drosophila model of SCA3, and one was confirmed as a key modulator of physiological ATXN3 abundance in SCA3 neuronal progenitor cells. ... Among identified pathways highlighted by this screen, the FBXL3/SCF axis represents a novel molecular pathway that regulates physiological levels of ATXN3 protein."
Friday, June 28, 2019
Automated tracking of leg movement in free-moving flies contributes to characterization of fly models of neurodegenerative diseases
Wu S, Tan KJ, Govindarajan LN, Stewart JC, Gu L, Ho JWH, Katarya M, Wong BH, Tan EK, Li D, Claridge-Chang A, Libedinsky C, Cheng L, Aw SS. Fully automated leg tracking of Drosophila neurodegeneration models reveals distinct conserved movement signatures. PLoS Biol. 2019 Jun 27;17(6):e3000346. PubMed PMID: 31246996.
Abstract: "Some neurodegenerative diseases, like Parkinsons Disease (PD) and Spinocerebellar ataxia 3 (SCA3), are associated with distinct, altered gait and tremor movements that are reflective of the underlying disease etiology. Drosophila melanogaster models of neurodegeneration have illuminated our understanding of the molecular mechanisms of disease. However, it is unknown whether specific gait and tremor dysfunctions also occur in fly disease mutants. To answer this question, we developed a machine-learning image-analysis program, Feature Learning-based LImb segmentation and Tracking (FLLIT), that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, producing a series of gait measurements. Notably, unlike other machine-learning methods, FLLIT generates its own training sets and does not require user-annotated images for learning. Using FLLIT, we carried out high-throughput and high-resolution analysis of gait and tremor features in Drosophila neurodegeneration mutants for the first time. We found that fly models of PD and SCA3 exhibited markedly different walking gait and tremor signatures, which recapitulated characteristics of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to a gait signature that more closely resembled those of PD flies. This suggests that the behavioral phenotype depends on the neurons affected rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits were affected. Using this approach, fly models can be used to dissect the neurogenetic mechanisms that underlie movement disorders."
Abstract: "Some neurodegenerative diseases, like Parkinsons Disease (PD) and Spinocerebellar ataxia 3 (SCA3), are associated with distinct, altered gait and tremor movements that are reflective of the underlying disease etiology. Drosophila melanogaster models of neurodegeneration have illuminated our understanding of the molecular mechanisms of disease. However, it is unknown whether specific gait and tremor dysfunctions also occur in fly disease mutants. To answer this question, we developed a machine-learning image-analysis program, Feature Learning-based LImb segmentation and Tracking (FLLIT), that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, producing a series of gait measurements. Notably, unlike other machine-learning methods, FLLIT generates its own training sets and does not require user-annotated images for learning. Using FLLIT, we carried out high-throughput and high-resolution analysis of gait and tremor features in Drosophila neurodegeneration mutants for the first time. We found that fly models of PD and SCA3 exhibited markedly different walking gait and tremor signatures, which recapitulated characteristics of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to a gait signature that more closely resembled those of PD flies. This suggests that the behavioral phenotype depends on the neurons affected rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits were affected. Using this approach, fly models can be used to dissect the neurogenetic mechanisms that underlie movement disorders."
Saturday, April 20, 2019
Reports related to neurodegenerative and neuromuscular disorders
Bondar VV, Adamski CJ, Onur TS, Tan Q, Wang L, Diaz-Garcia J, Park J, Orr HT, Botas J, Zoghbi HY. PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1. Hum Mol Genet. 2018 Aug 15;27(16):2863-2873.PMID: 29860311; PMCID: PMC6077814.
From the abstract: "... Loss-of-function of fly Pak3 or Pak1, whose mammalian homologs belong to Group I of PAK proteins, reduces ATXN1 levels, and accordingly, improves disease pathology in a Drosophila model of SCA1. Knockdown of PAK1 potently reduces ATXN1 levels in mammalian cells ... this study identifies PAK signaling as a distinct molecular pathway that regulates ATXN1 levels and presents a promising opportunity to pursue for developing potential therapeutics for SCA1."
Adusumalli S, Ngian ZK, Lin WQ, Benoukraf T, Ong CT. Increased intron retention is a post-transcriptional signature associated with progressive aging and Alzheimer's disease. Aging Cell. 2019 Mar 13:e12928. PMID: 30868713.
From the abstract: "Intron retention (IR) by alternative splicing is a conserved regulatory mechanism that can affect gene expression and protein function during adult development and age-onset diseases. ... By profiling the transcriptome of Drosophila head cells at different ages, we observed a significant increase in IR events for many genes during aging. ... our results suggest that an increased IR is an conserved signature that is associated with aging. ... changes of IR pattern during aging may regulate the transition from healthy to pathological state in late-onset sporadic AD."
Wang TH, Wang SY, Wang XD, Jiang HQ, Yang YQ, Wang Y, Cheng JL, Zhang CT, Liang WW, Feng HL. Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK. Neuroscience. 2018 May 21;379:152-166. PMID: 29559385.
From the abstract: "Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS) ... Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. ... Three different hSOD1-related mutant models were used ... results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations ... providing a potential treatment for ALS."
Lakkappa N, Krishnamurthy PT, M D P, Hammock BD, Hwang SH. Soluble epoxide hydrolase inhibitor, APAU, protects dopaminergic neurons against rotenone induced neurotoxicity: Implications for Parkinson's disease. Neurotoxicology. 2019 Jan;70:135-145. PMID: 30472438.
From the abstract: "Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, play a crucial role in cytoprotection by attenuating oxidative stress, inflammation and apoptosis. EETs are rapidly metabolised in vivo by the soluble epoxide hydrolase (sEH). Increasing the half life of EETs by inhibiting the sEH enzyme is a novel strategy for neuroprotection. ... sEH inhibitors APAU was screened in silico and further evaluated for their antiparkinson activity against rotenone (ROT) induced neurodegeneration in N27 dopaminergic cell line and Drosophila melanogaster model of Parkinson disease (PD). ..."
Krench M, Cho RW, Littleton JT. A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease. Hum Mol Genet. 2016 Aug 1;25(15):3164-3177. PMID: 27288455; PMCID: PMC5179919.
From the abstract: "Huntington disease-like 2 (HDL2) and Huntington disease (HD) are adult-onset neurodegenerative diseases ... we generated and characterized a Drosophila HDL2 model and compared it with a previously established HD model. We find that neuronal expression of HDL2-Q15 is not toxic, while the expression of an expanded HDL2-Q138 protein is lethal. HDL2-Q138 forms large nuclear aggregates, with only smaller puncta observed in the cytoplasm. This is in contrast to what is observed in a Drosophila model of HD, where polyQ aggregates localize exclusively to the cytoplasm. ... We conclude that while HD and HDL2 have similar clinical profiles, distinct pathogenic mechanisms are likely to drive toxicity in Drosophila models of these disorders."
Poska H, Haslbeck M, Kurudenkandy FR, Hermansson E, Chen G, Kostallas G, Abelein A, Biverstål H, Crux S, Fisahn A, Presto J, Johansson J. Dementia-related Bri2 BRICHOS is a versatile molecular chaperone that efficiently inhibits Aβ42 toxicity in Drosophila. Biochem J. 2016 Oct 15;473(20):3683-3704. PMID: 27514716.
From the abstract: "Formation of fibrils of the amyloid-β peptide (Aβ) is suggested to play a central role in neurodegeneration in Alzheimer's disease (AD), for which no effective treatment exists. The BRICHOS domain is a part of several disease-related proproteins ... we find that transgenic expression of the Bri2 BRICHOS domain in the Drosophila central nervous system (CNS) or eyes efficiently inhibits Aβ42 toxicity. ... These findings suggest that Bri2 BRICHOS can be a physiologically relevant chaperone for Aβ in the CNS ..."
From the abstract: "... Loss-of-function of fly Pak3 or Pak1, whose mammalian homologs belong to Group I of PAK proteins, reduces ATXN1 levels, and accordingly, improves disease pathology in a Drosophila model of SCA1. Knockdown of PAK1 potently reduces ATXN1 levels in mammalian cells ... this study identifies PAK signaling as a distinct molecular pathway that regulates ATXN1 levels and presents a promising opportunity to pursue for developing potential therapeutics for SCA1."
Adusumalli S, Ngian ZK, Lin WQ, Benoukraf T, Ong CT. Increased intron retention is a post-transcriptional signature associated with progressive aging and Alzheimer's disease. Aging Cell. 2019 Mar 13:e12928. PMID: 30868713.
From the abstract: "Intron retention (IR) by alternative splicing is a conserved regulatory mechanism that can affect gene expression and protein function during adult development and age-onset diseases. ... By profiling the transcriptome of Drosophila head cells at different ages, we observed a significant increase in IR events for many genes during aging. ... our results suggest that an increased IR is an conserved signature that is associated with aging. ... changes of IR pattern during aging may regulate the transition from healthy to pathological state in late-onset sporadic AD."
Wang TH, Wang SY, Wang XD, Jiang HQ, Yang YQ, Wang Y, Cheng JL, Zhang CT, Liang WW, Feng HL. Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK. Neuroscience. 2018 May 21;379:152-166. PMID: 29559385.
From the abstract: "Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS) ... Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. ... Three different hSOD1-related mutant models were used ... results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations ... providing a potential treatment for ALS."
Lakkappa N, Krishnamurthy PT, M D P, Hammock BD, Hwang SH. Soluble epoxide hydrolase inhibitor, APAU, protects dopaminergic neurons against rotenone induced neurotoxicity: Implications for Parkinson's disease. Neurotoxicology. 2019 Jan;70:135-145. PMID: 30472438.
From the abstract: "Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, play a crucial role in cytoprotection by attenuating oxidative stress, inflammation and apoptosis. EETs are rapidly metabolised in vivo by the soluble epoxide hydrolase (sEH). Increasing the half life of EETs by inhibiting the sEH enzyme is a novel strategy for neuroprotection. ... sEH inhibitors APAU was screened in silico and further evaluated for their antiparkinson activity against rotenone (ROT) induced neurodegeneration in N27 dopaminergic cell line and Drosophila melanogaster model of Parkinson disease (PD). ..."
Krench M, Cho RW, Littleton JT. A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease. Hum Mol Genet. 2016 Aug 1;25(15):3164-3177. PMID: 27288455; PMCID: PMC5179919.
From the abstract: "Huntington disease-like 2 (HDL2) and Huntington disease (HD) are adult-onset neurodegenerative diseases ... we generated and characterized a Drosophila HDL2 model and compared it with a previously established HD model. We find that neuronal expression of HDL2-Q15 is not toxic, while the expression of an expanded HDL2-Q138 protein is lethal. HDL2-Q138 forms large nuclear aggregates, with only smaller puncta observed in the cytoplasm. This is in contrast to what is observed in a Drosophila model of HD, where polyQ aggregates localize exclusively to the cytoplasm. ... We conclude that while HD and HDL2 have similar clinical profiles, distinct pathogenic mechanisms are likely to drive toxicity in Drosophila models of these disorders."
Poska H, Haslbeck M, Kurudenkandy FR, Hermansson E, Chen G, Kostallas G, Abelein A, Biverstål H, Crux S, Fisahn A, Presto J, Johansson J. Dementia-related Bri2 BRICHOS is a versatile molecular chaperone that efficiently inhibits Aβ42 toxicity in Drosophila. Biochem J. 2016 Oct 15;473(20):3683-3704. PMID: 27514716.
From the abstract: "Formation of fibrils of the amyloid-β peptide (Aβ) is suggested to play a central role in neurodegeneration in Alzheimer's disease (AD), for which no effective treatment exists. The BRICHOS domain is a part of several disease-related proproteins ... we find that transgenic expression of the Bri2 BRICHOS domain in the Drosophila central nervous system (CNS) or eyes efficiently inhibits Aβ42 toxicity. ... These findings suggest that Bri2 BRICHOS can be a physiologically relevant chaperone for Aβ in the CNS ..."
Thursday, January 31, 2019
Genetic screen in flies helps elucidate cellular mechanisms of spinocerebellar ataxia type 3 (SCA3)
Chen ZS, Wong AKY, Cheng TC, Koon AC, Chan HYE. FipoQ/FBXO33, a Cullin-1 based ubiquitin ligase complex component modulates ubiquitination and solubility of polyglutamine disease protein. J Neurochem. 2019 Jan 26. doi: 10.1111/jnc.14669. PubMed PMID: 30685895.
From the abstract: "Polyglutamine (polyQ) diseases describe a group of progressive neurodegenerative disorders ... To date, nine such diseases, including spinocerebellar ataxia type 3 (SCA3), have been reported. The formation of SDS-insoluble protein aggregates in neurons causes cellular dysfunctions, such as impairment of the ubiquitin-proteasome system (UPS), and contributes to polyQ pathologies. Recently, the E3 ubiquitin ligases, which govern substrate specificity of the UPS, have been implicated in polyQ pathogenesis. The Cullin (Cul) proteins are major components of Cullin-RING ubiquitin ligases (CRLs) complexes that are evolutionarily conserved in the Drosophila genome. In this study, we examined the effect of individual Culs on SCA3 pathogenesis ... We further performed a genetic modifier screen of the 19 Drosophila F-box genes, and identified F-box involved in polyQ pathogenesis (FipoQ) as a genetic modifier of SCA3 degeneration ... In the human SK-N-MC cell model, we identified F-box only protein 33 (FBXO33) exerts similar functions as FipoQ ... These findings will lead to a better understanding of the disease mechanism of SCA3, and provide insights on developing treatments against SCA3."
From the abstract: "Polyglutamine (polyQ) diseases describe a group of progressive neurodegenerative disorders ... To date, nine such diseases, including spinocerebellar ataxia type 3 (SCA3), have been reported. The formation of SDS-insoluble protein aggregates in neurons causes cellular dysfunctions, such as impairment of the ubiquitin-proteasome system (UPS), and contributes to polyQ pathologies. Recently, the E3 ubiquitin ligases, which govern substrate specificity of the UPS, have been implicated in polyQ pathogenesis. The Cullin (Cul) proteins are major components of Cullin-RING ubiquitin ligases (CRLs) complexes that are evolutionarily conserved in the Drosophila genome. In this study, we examined the effect of individual Culs on SCA3 pathogenesis ... We further performed a genetic modifier screen of the 19 Drosophila F-box genes, and identified F-box involved in polyQ pathogenesis (FipoQ) as a genetic modifier of SCA3 degeneration ... In the human SK-N-MC cell model, we identified F-box only protein 33 (FBXO33) exerts similar functions as FipoQ ... These findings will lead to a better understanding of the disease mechanism of SCA3, and provide insights on developing treatments against SCA3."
Tuesday, August 28, 2018
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."
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."
Monday, June 4, 2018
Fly model contributes to understanding of spinocerebellar ataxia type 1
Bondar VV, Adamski CJ, Onur TS, Tan Q, Wang L, Diaz-Garcia J, Park J, Orr HT, Botas J, Zoghbi HY. PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in Spinocerebellar ataxia type 1. Hum Mol Genet. 2018 May 30. PMID: 29860311.
The abstract: "Spinocerebellar ataxia type 1 (SCA1) is caused by the expansion of a trinucleotide repeat that encodes a polyglutamine tract in ataxin-1 (ATXN1). The expanded polygultamine in ATXN1 increases the protein's stability and results in its accumulation and toxicity. Previous studies have demonstrated that decreasing ATXN1 levels ameliorates SCA1 phenotypes and pathology in mouse models. We rationalized that reducing ATXN1 levels through pharmacological inhibition of its modulators could provide a therapeutic avenue for SCA1. Here, through a forward genetic screen in Drosophila we identified, p21-activated kinase 3 (Pak3) as a modulator of ATXN1 levels. Loss-of-function of fly Pak3 and Pak1, whose mammalian homologs are Group I of PAKs, reduces ATXN1 levels, and accordingly, improves disease pathology in a Drosophila model of SCA1. Knockdown of PAK1 potently reduces ATXN1 levels in mammalian cells independent of the well-characterized S776 phosphorylation site (known to stabilize ATXN1) thus revealing a novel molecular pathway that regulates ATXN1 levels. Furthermore, pharmacological inhibition of PAKs decreases ATXN1 levels in a mouse model of SCA1. To explore the potential of using PAK inhibitors in combination therapy, we combined the pharmacological inhibition of PAK with MSK1, a previously identified modulator of ATXN1, and examined their effects on ATXN1 levels. We found that inhibition of both pathways results in an additive decrease in ATXN1 levels. Together, this study identifies PAK signaling as a distinct molecular pathway that regulates ATXN1 levels and presents a promising opportunity to pursue for developing potential therapeutics for SCA1."
The abstract: "Spinocerebellar ataxia type 1 (SCA1) is caused by the expansion of a trinucleotide repeat that encodes a polyglutamine tract in ataxin-1 (ATXN1). The expanded polygultamine in ATXN1 increases the protein's stability and results in its accumulation and toxicity. Previous studies have demonstrated that decreasing ATXN1 levels ameliorates SCA1 phenotypes and pathology in mouse models. We rationalized that reducing ATXN1 levels through pharmacological inhibition of its modulators could provide a therapeutic avenue for SCA1. Here, through a forward genetic screen in Drosophila we identified, p21-activated kinase 3 (Pak3) as a modulator of ATXN1 levels. Loss-of-function of fly Pak3 and Pak1, whose mammalian homologs are Group I of PAKs, reduces ATXN1 levels, and accordingly, improves disease pathology in a Drosophila model of SCA1. Knockdown of PAK1 potently reduces ATXN1 levels in mammalian cells independent of the well-characterized S776 phosphorylation site (known to stabilize ATXN1) thus revealing a novel molecular pathway that regulates ATXN1 levels. Furthermore, pharmacological inhibition of PAKs decreases ATXN1 levels in a mouse model of SCA1. To explore the potential of using PAK inhibitors in combination therapy, we combined the pharmacological inhibition of PAK with MSK1, a previously identified modulator of ATXN1, and examined their effects on ATXN1 levels. We found that inhibition of both pathways results in an additive decrease in ATXN1 levels. Together, this study identifies PAK signaling as a distinct molecular pathway that regulates ATXN1 levels and presents a promising opportunity to pursue for developing potential therapeutics for SCA1."
Thursday, December 15, 2016
Catching up on Drosophila papers related to neurodegenerative disease--research reports and a review
Alzheimer's disease
Liu QF, Lee JH, Kim YM, Lee S, Hong YK, Hwang S, Oh Y, Lee K, Yun HS, Lee IS, Jeon S, Chin YW, Koo BS, Cho KS. In Vivo Screening of Traditional Medicinal Plants for Neuroprotective Activity against Aβ42 Cytotoxicity by Using Drosophila Models of Alzheimer's Disease. Biol Pharm Bull. 2015;38(12):1891-901. PMID: 26458335.
Wang X, Perumalsamy H, Kwon HW, Na YE, Ahn YJ. Effects and possible mechanisms of action of acacetin on the behavior and eye morphology of Drosophila models of Alzheimer's disease. Sci Rep. 2015 Nov 4;5:16127. PMID: 26530776; PMCID: PMC4632086.
Kong Y, Wu J, Zhang D, Wan C, Yuan L. The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway. Curr Mol Med. 2015;15(10):980-9. PubMed PMID: 26592243.
Peng F, Zhao Y, Huang X, Chen C, Sun L, Zhuang L, Xue L. Loss of Polo ameliorates APP-induced Alzheimer's disease-like symptoms in Drosophila. Sci Rep. 2015 Nov 24;5:16816. PMID: 26597721; PMCID: PMC4657023.
Geng J, Xia L, Li W, Zhao C, Dou F. Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells. J Alzheimers Dis. 2016;49(4):1161-8. PMID: 26599052; PMCID: PMC4927919.
Haddadi M, Nongthomba U, Jahromi SR, Ramesh SR. Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration. Behav Brain Res. 2016 Mar 15;301:10-8. PMID: 26706888.
Wang X, Ma Y, Zhao Y, Chen Y, Hu Y, Chen C, Shao Y, Xue L. APLP1 promotes dFoxO-dependent cell death in Drosophila. Apoptosis. 2015 Jun;20(6):778-86. PMID: 25740230.
Lau HC, Lee IK, Ko PW, Lee HW, Huh JS, Cho WJ, Lim JO. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor. PLoS One. 2015 Feb 25;10(2):e0117810. PMID: 25714733; PMCID: PMC4340960.
Frenkel-Pinter M, Tal S, Scherzer-Attali R, Abu-Hussien M, Alyagor I, Eisenbaum T, Gazit E, Segal D. Naphthoquinone-Tryptophan Hybrid Inhibits Aggregation of the Tau-Derived Peptide PHF6 and Reduces Neurotoxicity. J Alzheimers Dis. 2016;51(1):165-78. PMID: 26836184.
ALS
Chai A, Pennetta G. Insights into ALS pathomechanisms: from flies to humans. Fly (Austin). 2015;9(2):91-8. PMID: 26594942; PMCID: PMC4826116. ---REVIEW
Cragnaz L, Klima R, De Conti L, Romano G, Feiguin F, Buratti E, Baralle M, Baralle FE. An age-related reduction of brain TBPH/TDP-43 levels precedes the onset of locomotion defects in a Drosophila ALS model. Neuroscience. 2015 Dec 17;311:415-21. PMID: 26518462.
Xia Q, Wang H, Hao Z, Fu C, Hu Q, Gao F, Ren H, Chen D, Han J, Ying Z, Wang G. TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion. EMBO J. 2016 Jan 18;35(2):121-42. PMID: 26702100; PMCID: PMC4718457.
Romano M, Feiguin F, Buratti E. TBPH/TDP-43 modulates translation of Drosophila futsch mRNA through an UG-rich sequence within its 5'UTR. Brain Res. 2016 Sep 15;1647:50-6. doi: 10.1016/j.brainres.2016.02.022. PubMed PMID: 26902497.
FTD/ALS
Tran H, Almeida S, Moore J, Gendron TF, Chalasani U, Lu Y, Du X, Nickerson JA, Petrucelli L, Weng Z, Gao FB. Differential Toxicity of Nuclear RNA Foci versus Dipeptide Repeat Proteins in a Drosophila Model of C9ORF72 FTD/ALS. Neuron. 2015 Sep 23;87(6):1207-14. PMID: 26402604; PMCID: PMC4589299.
Parkinson's disease
West RJ, Elliott CJ, Wade AR. Classification of Parkinson's Disease Genotypes in Drosophila Using Spatiotemporal Profiling of Vision. Sci Rep. 2015 Nov 24;5:16933. PMID: 26597171; PMCID: PMC4657034.
Gao F, Chen D, Si J, Hu Q, Qin Z, Fang M, Wang G. The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum Mol Genet. 2015 May 1;24(9):2528-38. PMID: 25612572.
Vos M, Verstreken P, Klein C. Stimulation of electron transport as potential novel therapy in Parkinson's disease with mitochondrial dysfunction. Biochem Soc Trans. 2015 Apr;43(2):275-9. PMID: 25849929.
Wiemerslage L, Lee D. Quantification of mitochondrial morphology in neurites of dopaminergic neurons using multiple parameters. J Neurosci Methods. 2016 Mar 15;262:56-65. PMID: 26777473; PMCID: PMC4775301. ---PROTOCOL
Langston RG, Rudenko IN, Cookson MR. The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research. Biochem J. 2016 Feb 1;473(3):221-32. PMID: 26811536.
Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu KY, Nukina N, Hattori N, Imai Y. Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet. 2014 Dec 4;10(12):e1004861. PMID: 25474007; PMCID: PMC4256268.
HD, AD & PD
Poças GM, Branco-Santos J, Herrera F, Outeiro TF, Domingos PM. α-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila. Hum Mol Genet. 2015 Apr 1;24(7):1898-907. PMID: 25452431; PMCID: PMC4355023.
Stroedicke M, Bounab Y, Strempel N, Klockmeier K, Yigit S, Friedrich RP, Chaurasia G, Li S, Hesse F, Riechers SP, Russ J, Nicoletti C, Boeddrich A, Wiglenda T, Haenig C, Schnoegl S, Fournier D, Graham RK, Hayden MR, Sigrist S, Bates GP, Priller J, Andrade-Navarro MA, Futschik ME, Wanker EE. Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity. Genome Res. 2015 May;25(5):701-13. PMID: 25908449; PMCID: PMC4417118.
Spinal Cerebellar Ataxia
Blount JR, Tsou WL, Ristic G, Burr AA, Ouyang M, Galante H, Scaglione KM, Todi SV. Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23. Nat Commun. 2014 Aug 21;5:4638. PMID: 25144244; PMCID: PMC4237202.
Prion disease
Steinert JR. Prion protein as a mediator of synaptic transmission. Commun Integr Biol. 2015 Aug 14;8(4):e1063753. PMID: 26478992; PMCID: PMC4594542.
Liu QF, Lee JH, Kim YM, Lee S, Hong YK, Hwang S, Oh Y, Lee K, Yun HS, Lee IS, Jeon S, Chin YW, Koo BS, Cho KS. In Vivo Screening of Traditional Medicinal Plants for Neuroprotective Activity against Aβ42 Cytotoxicity by Using Drosophila Models of Alzheimer's Disease. Biol Pharm Bull. 2015;38(12):1891-901. PMID: 26458335.
Wang X, Perumalsamy H, Kwon HW, Na YE, Ahn YJ. Effects and possible mechanisms of action of acacetin on the behavior and eye morphology of Drosophila models of Alzheimer's disease. Sci Rep. 2015 Nov 4;5:16127. PMID: 26530776; PMCID: PMC4632086.
Kong Y, Wu J, Zhang D, Wan C, Yuan L. The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway. Curr Mol Med. 2015;15(10):980-9. PubMed PMID: 26592243.
Peng F, Zhao Y, Huang X, Chen C, Sun L, Zhuang L, Xue L. Loss of Polo ameliorates APP-induced Alzheimer's disease-like symptoms in Drosophila. Sci Rep. 2015 Nov 24;5:16816. PMID: 26597721; PMCID: PMC4657023.
Geng J, Xia L, Li W, Zhao C, Dou F. Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells. J Alzheimers Dis. 2016;49(4):1161-8. PMID: 26599052; PMCID: PMC4927919.
Haddadi M, Nongthomba U, Jahromi SR, Ramesh SR. Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration. Behav Brain Res. 2016 Mar 15;301:10-8. PMID: 26706888.
Wang X, Ma Y, Zhao Y, Chen Y, Hu Y, Chen C, Shao Y, Xue L. APLP1 promotes dFoxO-dependent cell death in Drosophila. Apoptosis. 2015 Jun;20(6):778-86. PMID: 25740230.
Lau HC, Lee IK, Ko PW, Lee HW, Huh JS, Cho WJ, Lim JO. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor. PLoS One. 2015 Feb 25;10(2):e0117810. PMID: 25714733; PMCID: PMC4340960.
Frenkel-Pinter M, Tal S, Scherzer-Attali R, Abu-Hussien M, Alyagor I, Eisenbaum T, Gazit E, Segal D. Naphthoquinone-Tryptophan Hybrid Inhibits Aggregation of the Tau-Derived Peptide PHF6 and Reduces Neurotoxicity. J Alzheimers Dis. 2016;51(1):165-78. PMID: 26836184.
ALS
Chai A, Pennetta G. Insights into ALS pathomechanisms: from flies to humans. Fly (Austin). 2015;9(2):91-8. PMID: 26594942; PMCID: PMC4826116. ---REVIEW
Cragnaz L, Klima R, De Conti L, Romano G, Feiguin F, Buratti E, Baralle M, Baralle FE. An age-related reduction of brain TBPH/TDP-43 levels precedes the onset of locomotion defects in a Drosophila ALS model. Neuroscience. 2015 Dec 17;311:415-21. PMID: 26518462.
Xia Q, Wang H, Hao Z, Fu C, Hu Q, Gao F, Ren H, Chen D, Han J, Ying Z, Wang G. TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion. EMBO J. 2016 Jan 18;35(2):121-42. PMID: 26702100; PMCID: PMC4718457.
Romano M, Feiguin F, Buratti E. TBPH/TDP-43 modulates translation of Drosophila futsch mRNA through an UG-rich sequence within its 5'UTR. Brain Res. 2016 Sep 15;1647:50-6. doi: 10.1016/j.brainres.2016.02.022. PubMed PMID: 26902497.
FTD/ALS
Tran H, Almeida S, Moore J, Gendron TF, Chalasani U, Lu Y, Du X, Nickerson JA, Petrucelli L, Weng Z, Gao FB. Differential Toxicity of Nuclear RNA Foci versus Dipeptide Repeat Proteins in a Drosophila Model of C9ORF72 FTD/ALS. Neuron. 2015 Sep 23;87(6):1207-14. PMID: 26402604; PMCID: PMC4589299.
Parkinson's disease
West RJ, Elliott CJ, Wade AR. Classification of Parkinson's Disease Genotypes in Drosophila Using Spatiotemporal Profiling of Vision. Sci Rep. 2015 Nov 24;5:16933. PMID: 26597171; PMCID: PMC4657034.
Gao F, Chen D, Si J, Hu Q, Qin Z, Fang M, Wang G. The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum Mol Genet. 2015 May 1;24(9):2528-38. PMID: 25612572.
Vos M, Verstreken P, Klein C. Stimulation of electron transport as potential novel therapy in Parkinson's disease with mitochondrial dysfunction. Biochem Soc Trans. 2015 Apr;43(2):275-9. PMID: 25849929.
Wiemerslage L, Lee D. Quantification of mitochondrial morphology in neurites of dopaminergic neurons using multiple parameters. J Neurosci Methods. 2016 Mar 15;262:56-65. PMID: 26777473; PMCID: PMC4775301. ---PROTOCOL
Langston RG, Rudenko IN, Cookson MR. The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research. Biochem J. 2016 Feb 1;473(3):221-32. PMID: 26811536.
Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu KY, Nukina N, Hattori N, Imai Y. Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet. 2014 Dec 4;10(12):e1004861. PMID: 25474007; PMCID: PMC4256268.
HD, AD & PD
Poças GM, Branco-Santos J, Herrera F, Outeiro TF, Domingos PM. α-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila. Hum Mol Genet. 2015 Apr 1;24(7):1898-907. PMID: 25452431; PMCID: PMC4355023.
Stroedicke M, Bounab Y, Strempel N, Klockmeier K, Yigit S, Friedrich RP, Chaurasia G, Li S, Hesse F, Riechers SP, Russ J, Nicoletti C, Boeddrich A, Wiglenda T, Haenig C, Schnoegl S, Fournier D, Graham RK, Hayden MR, Sigrist S, Bates GP, Priller J, Andrade-Navarro MA, Futschik ME, Wanker EE. Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity. Genome Res. 2015 May;25(5):701-13. PMID: 25908449; PMCID: PMC4417118.
Spinal Cerebellar Ataxia
Blount JR, Tsou WL, Ristic G, Burr AA, Ouyang M, Galante H, Scaglione KM, Todi SV. Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23. Nat Commun. 2014 Aug 21;5:4638. PMID: 25144244; PMCID: PMC4237202.
Prion disease
Steinert JR. Prion protein as a mediator of synaptic transmission. Commun Integr Biol. 2015 Aug 14;8(4):e1063753. PMID: 26478992; PMCID: PMC4594542.
Monday, February 15, 2016
New fly model of SMA type 6
Tsou WL, Hosking RR, Burr AA, Sutton JR, Ouyang M, Du X, Gomez CM, Todi SV. DnaJ-1 and karyopherin α3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6. Hum Mol Genet. 2015 Aug 1;24(15):4385-96. PMID: 25954029; PMCID: PMC4492400.
Friday, July 17, 2015
New fly models of Spinocerebellar ataxia type 17
Hsu TC, Wang CK, Yang CY, Lee LC, Hsieh-Li HM, Ro LS, Chen CM, Lee-Chen GJ, Su MT. Deactivation of TBP contributes to SCA17 pathogenesis. Hum Mol Genet. 2014 Dec 20;23(25):6878-93. PMID: 25104854.
From the abstract: "Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). ... In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. ... downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration. "
From the abstract: "Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). ... In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. ... downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration. "
Friday, January 23, 2015
Drosophila genetic analysis contributes to study on Gordon Holmes syndrome (GDHS)
Topaloglu AK, Lomniczi A, Kretzschmar D, Dissen GA, Kotan LD, McArdle CA, Koc AF, Hamel BC, Guclu M, Papatya ED, Eren E, Mengen E, Gurbuz F, Cook M, Castellano JM, Kekil MB, Mungan NO, Yuksel B, Ojeda SR. Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. J Clin Endocrinol Metab. 2014 Oct;99(10):E2067-75. PMID: 25033069.
From the abstract: "... We identified 6 patients from 3 independent families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE) ... Wild-type PNPLA6, but not PNPLA6 bearing these mutations, rescued a well-established Drosophila neurodegenerative phenotype caused by the absence of sws, the fly ortholog of mammalian PNPLA6. ..."
From the abstract: "... We identified 6 patients from 3 independent families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE) ... Wild-type PNPLA6, but not PNPLA6 bearing these mutations, rescued a well-established Drosophila neurodegenerative phenotype caused by the absence of sws, the fly ortholog of mammalian PNPLA6. ..."
Saturday, September 27, 2014
Fly study related to spincerebellar ataxia
Liman J, Deeg S, Voigt A, Voßfeldt H, Dohm CP, Karch A, Weishaupt J, Schulz JB, Bähr M, Kermer P. CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration. J Neurochem. 2014 Jun;129(6):1013-23. PMID: 24548080.
Monday, June 2, 2014
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.
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.
Thursday, May 8, 2014
Two papers--flies and neurodegenerative disease--including a fluorescent protein-based fly eye assay
There are more papers to catch up on but in the meantime, these caught my eye today:
Rumpf S, Bagley JA, Thompson-Peer KL, Zhu S, Gorczyca D, Beckstead RB, Jan LY, Jan YN. Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism. Proc Natl Acad Sci U S A. 2014 May 5. PMID: 24799714.
Burr AA, Tsou WL, Ristic G, Todi SV. Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila Eyes. J Neurosci Res. 2014 May 2. PMID: 24798551. From the abstract: "Here, we describe a sensitive fluorescence-based method to observe, monitor, and quantify mild Drosophila eye degeneration caused by various proteins, including the polyglutamine disease proteins ataxin-3 (spinocerebellar ataxia type 3) and huntingtin (Huntington's disease), mutant α-synuclein (Parkinson's disease), and Aβ42 (Alzheimer's disease). We show that membrane-targeted green fluorescent protein reports degeneration robustly and quantitatively. This simple yet powerful technique, which is amenable to large-scale screens, can help accelerate studies to understand age-related degeneration and to find factors that suppress it for therapeutic purposes."
Rumpf S, Bagley JA, Thompson-Peer KL, Zhu S, Gorczyca D, Beckstead RB, Jan LY, Jan YN. Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism. Proc Natl Acad Sci U S A. 2014 May 5. PMID: 24799714.
Burr AA, Tsou WL, Ristic G, Todi SV. Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila Eyes. J Neurosci Res. 2014 May 2. PMID: 24798551. From the abstract: "Here, we describe a sensitive fluorescence-based method to observe, monitor, and quantify mild Drosophila eye degeneration caused by various proteins, including the polyglutamine disease proteins ataxin-3 (spinocerebellar ataxia type 3) and huntingtin (Huntington's disease), mutant α-synuclein (Parkinson's disease), and Aβ42 (Alzheimer's disease). We show that membrane-targeted green fluorescent protein reports degeneration robustly and quantitatively. This simple yet powerful technique, which is amenable to large-scale screens, can help accelerate studies to understand age-related degeneration and to find factors that suppress it for therapeutic purposes."
Monday, April 28, 2014
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.
Sunday, March 30, 2014
Suppression of degeneration in a fly model of spinocerebellar ataxia
Cushman-Nick M, Bonini NM, Shorter J. Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model. PLoS Genet. 2013;9(9):e1003781. PMID: 24039611; PMCID: PMC3764203.
Friday, September 6, 2013
Integrated approach to spinocerebellar ataxia includes Drosophila genetic screens
Park J, Al-Ramahi I, Tan Q, Mollema N, Diaz-Garcia JR, Gallego-Flores T, Lu HC, Lagalwar S, Duvick L, Kang H, Lee Y, Jafar-Nejad P, Sayegh LS, Richman R, Liu X, Gao Y, Shaw CA, Arthur JS, Orr HT, Westbrook TF, Botas J, Zoghbi HY. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013 Jun 20;498(7454):325-31. PMID: 23719381.
From the abstract: "We have developed a strategy to identify therapeutic entry points ... this approach, which integrates parallel cell-based and Drosophila genetic screens, ... revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice."
From the abstract: "We have developed a strategy to identify therapeutic entry points ... this approach, which integrates parallel cell-based and Drosophila genetic screens, ... revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice."
Monday, August 5, 2013
Pre-clinical drug trial for disease with currently "no disease-modifying treatments" includes Drosophila studies
This study focuses on Spinocerebellar ataxia type 3 (SCA3), which the authors indicate is also known as Machado-Joseph Disease (MJD).
Yi J, Zhang L, Tang B, Han W, Zhou Y, Chen Z, Jia D, Jiang H. Sodium valproate alleviates neurodegeneration in SCA3/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4. PLoS One. 2013;8(1):e54792. PMID: 23382971; PMCID: PMC3557284.
Yi J, Zhang L, Tang B, Han W, Zhou Y, Chen Z, Jia D, Jiang H. Sodium valproate alleviates neurodegeneration in SCA3/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4. PLoS One. 2013;8(1):e54792. PMID: 23382971; PMCID: PMC3557284.
Monday, June 3, 2013
Using the fly to find genetic modifiers of polyglutamine-induced toxicity
VoSSfeldt H, Butzlaff M, PrüSSing K, Ní Chárthaigh RA, Karsten P, Lankes A, Hamm S, Simons M, Adryan B, Schulz JB, Voigt A. Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila. PLoS One. 2012;7(11):e47452. PMID: 23139745; PMCID: PMC3489908.
Mammalian Itpr1 can provide function in IP(3)R mutant flies. Recent report related to spinocerebellar ataxia.
Chakraborty S, Hasan G. Functional complementation of Drosophila itpr mutants by rat Itpr1. J Neurogenet. 2012 Sep;26(3-4):328-37. PMID: 22817477.
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