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Genetics and neuropathology strongly link α-synuclein aggregation and neurotoxicity to the pathogenesis of Parkinson's disease and related α-synucleinopathies. Here we describe a new Drosophila model of α-synucleinopathy based on widespread expression of wild-type human α-synuclein, which shows robust neurodegeneration, early-onset locomotor deficits, and abundant α-synuclein aggregation. We use results of forward genetic screening and genetic analysis in our new model to demonstrate that α-synuclein expression promotes reorganization of the actin filament network and consequent mitochondrial dysfunction through altered Drp1 localization. Similar changes are present in a mouse α-synucleinopathy model and in postmortem brain tissue from patients with α-synucleinopathy. Importantly, we provide evidence that the interaction of α-synuclein with spectrin initiates pathological alteration of the actin cytoskeleton and downstream neurotoxicity. These findings suggest new therapeutic approaches for α-synuclein induced neurodegeneration.
Pubmed ID: 29249285 RIS Download
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Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsImaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsCollects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.
View all literature mentionsThis recombinant polyclonal secondary targets IgG (Heavy Chain)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis recombinant polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets mouse IgG
View all literature mentionsThis monoclonal targets VDAC1 / Porin
View all literature mentionsThis monoclonal targets GAPDH Loading Control
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Microtubule-Associated Protein 2 (MAP2)
View all literature mentionsThis monoclonal targets Spectrin, alpha
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis monoclonal targets ATP5A1
View all literature mentionsThis monoclonal targets Mouse Drosophila elav protein
View all literature mentionsThis monoclonal targets Cleaved PARP antibody [E51]
View all literature mentionsThis polyclonal targets Cofilin
View all literature mentionsThis monoclonal targets & x03B2;-Galactosidase
View all literature mentionsThis monoclonal targets synuclein, alpha & beta
View all literature mentionsThis monoclonal targets Aggregated a-Synuclein.
View all literature mentionsThis monoclonal targets Actin
View all literature mentionsDiscontinued
View all literature mentionsMus musculus with name B6.Cg-2310039L15RikTg(Prnp-SNCA*A53T)23Mkle/J from IMSR.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=FLAG-FlAsH-HA-Drp1}3, Ki[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-MitoTimer}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01606}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ21037}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EGFP}5a.2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=10XUAS-mCD8::GFP}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=QUAS-mCD8-GFP.P}5B/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{y[+mDint2]=MIC}alpha-Spec[MI11816] dlt[MI11816]/TM3, Sb[1] Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; ru[1] alpha-Spec[rg41] st[1] e[s]/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; ru[1] alpha-Spec[lm88] st[1] e[s]/TM6B from BDSC.
View all literature mentionsDrosophila melanogaster with name w[67c23] P{w[+mC]=lacW}Act5C[G0010]/FM7c from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UASp-GFP.Act5C}2-1 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=ple-GAL4.F}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+mW.hs]=GawB}elav[C155] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=FLAG-FlAsH-HA-Drp1}3, Ki[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-MitoTimer}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01606}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ21037}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EGFP}5a.2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=10XUAS-mCD8::GFP}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=QUAS-mCD8-GFP.P}5B/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{y[+mDint2]=MIC}alpha-Spec[MI11816] dlt[MI11816]/TM3, Sb[1] Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; ru[1] alpha-Spec[rg41] st[1] e[s]/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; ru[1] alpha-Spec[lm88] st[1] e[s]/TM6B from BDSC.
View all literature mentionsDrosophila melanogaster with name w[67c23] P{w[+mC]=lacW}Act5C[G0010]/FM7c from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UASp-GFP.Act5C}2-1 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=ple-GAL4.F}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+mW.hs]=GawB}elav[C155] from BDSC.
View all literature mentionsDiscontinued
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EGFP}5a.2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=10XUAS-mCD8::GFP}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=QUAS-mCD8-GFP.P}5B/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{y[+mDint2]=MIC}alpha-Spec[MI11816] dlt[MI11816]/TM3, Sb[1] Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=ple-GAL4.F}3 from BDSC.
View all literature mentionsDiscontinued
View all literature mentionsDrosophila melanogaster with name P{w[+mW.hs]=GawB}elav[C155] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=FLAG-FlAsH-HA-Drp1}3, Ki[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-MitoTimer}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01606}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ21037}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; ru[1] alpha-Spec[rg41] st[1] e[s]/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; ru[1] alpha-Spec[lm88] st[1] e[s]/TM6B from BDSC.
View all literature mentionsDrosophila melanogaster with name w[67c23] P{w[+mC]=lacW}Act5C[G0010]/FM7c from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UASp-GFP.Act5C}2-1 from BDSC.
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